Case Rep Oncol 2015;8:179–184

DOI: 10.1159/000381451 © 2015 S. Karger AG, Basel

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A Case of Swyer Syndrome

Associated with Advanced Gonadal
Dysgerminoma Involving Long
Survival
Salete Da Silva Riosa Isabella Christina Mazzaro Monteiroa
Larissa Gonçalves Braz dos Santosa Natasha Garcia Caldas a
Ana Carolina Rios Chena Juliana Rios Chena
Helena Spindola Camargo Silva b
a b
Departments of Gynecology and Pathology, University of Brasília, Brasília, Brazil

Key Words
Swyer syndrome · Dysgerminoma · Gonadal tumor

Abstract
Swyer syndrome is caused by abnormal sex differentiation during the embryonic period,
resulting in incomplete intrauterine masculinization and undifferentiated gonads. The current
case report describes a patient with Swyer syndrome associated with stage 3 gonadal dys-
germinoma who has survived for 23 years. At age 18, this patient sought assistance for pri-
mary amenorrhea from the Gynecological Services Department of the University of Brasília
Hospital. A physical examination revealed that the patient was at Tanner stage 4 with respect
to axillary hair, breasts, and pubic hair; she presented with a eutrophic vagina and a small
cervix. She was treated with a combination of estrogens and progestogens to induce cycling.
Approximately 4 years later, a complex tumor was found and resected; a histopathological
analysis revealed that this tumor was a right adnexal dysgerminoma with peritoneal affection.
The patient was also subjected to chemotherapy. Her follow-up has continued to the present
time, with no signs of tumor recurrence. In conclusion, this report describes an extremely rare
case in which Swyer syndrome was associated with ovarian dysgerminoma; relative to similar
patients, the described patient has survived for an unusually prolonged time.
© 2015 S. Karger AG, Basel

Dr. Salete Rios, MD, PhD, MSc

Department of Gynecology, University of Brasília
Campus Universitário Darcy Ribeiro
CEP 70910-900 Brasília (Brazil)
E-Mail [email protected]
 Case Rep Oncol 2015;8:179–184
DOI: 10.1159/000381451 © 2015 S. Karger AG, Basel 180
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Da Silva Rios et al.: A Case of Swyer Syndrome Associated with Advanced Gonadal
Dysgerminoma Involving Long Survival

Introduction

Disorders of sex development (DSD) are congenital conditions characterized by atypical

chromosomal, gonadal, or anatomical sex development [1]. In 2006, a consensus statement
was issued that recommended the use of the DSD classification to replace various terms that
are no longer utilized, such as pseudohermaphrodite, intersex, and sex reversal, among oth-
ers [2]. Complete gonadal dysgenesis is characterized by a female phenotype, nonambiguous
genitalia, the presence of Müllerian derivatives, gonadal dysgenesis, and a normal karyotype
[3]. One type of gonadal dysgenesis is Swyer syndrome, which is a rare cause of DSD with an
incidence of 1:80,000. This syndrome, which was described by Swyer in 1955, is caused by
an error in sex determination during the course of embryogenesis. Patients with Swyer syn-
drome present with an incomplete masculinization due to deficiencies in the production of
testosterone and Müllerian-inhibiting factors that result in the failure of gonadal progression
[4]. Molecular and genetic abnormalities associated with this condition include mutations in
the ARX, ATRX, CBX2, DHH, DMRT1, GATA4, MAMLD1, MAP3K1, NR0B1 (which relates to
DAX1 expression and congenital adrenal hypoplasia), NR5A1 (which encodes steroidogenic
factor 1), SOX9, WNT4, WT1, WWOX, SRY, and WNT4 genes. The SRY gene is deleted in ap-
proximately 10–15% of patients with Swyer syndrome and mutated in an additional 10–
15% of Swyer syndrome patients [1, 3]. Most Swyer syndrome patients first seek medical
attention in adolescence for primary amenorrhea and/or the absence of secondary sex char-
acteristics [5].
Swyer syndrome patients are normal too, tall in height and present with small or unde-
veloped breasts, but normal axillary and pubic hair. The external genitalia are typical of fe-
males, the upper part of the vagina and tubes are normal or reduced in size, and the uterus is
small or rudimentary. The gonads are dysgenetic strips composed of only fibrous tissue;
they do not exhibit hormonal function, gametogenesis, or any structure that allows them to
be identified as either ovaries or testicles, although their karyotype is 46,XY. The gonads are
at high risk for gonadal tumors, which are typically gonadoblastomas and/or dysgermino-
mas [3, 4]. Dysgerminomas are generally rare, accounting for less than 5% of ovarian tu-
mors, but exhibit a high malignant potential [6]; however, this type of tumor is found in 1 out
of every 3 individuals with Swyer syndrome [7]. Dysgerminomas typically present with ab-
dominal pain (70–80%) and a lower abdominal mass [8].

Case Report

The patient first sought care at the Gynecological Services Department of the University
of Brasília Hospital at the age of 18 years for amenorrhea. She reported experiencing an ado-
lescent growth spurt at the age of 11 years and thelarche at the age of 16 years, with no per-
sonal history of disease. With respect to family history, she reported having a nulliparous
aunt with similar complaints who had been subjected to pharmacological treatment to in-
duce menstruation. Upon physical examination, the patient’s height was 1.69 m, and her
axillary hair, breasts, and pubic hair were consistent with Tanner stage 4. The vagina was
eutrophic, with physiological secretions. The cervix was small, although a large area of the
cervix was positively stained by the Schiller iodine test; this result indicates hypoestrogen-
ism. Laboratory tests produced the following results: follicle-stimulating hormone (FSH)
levels of 50 mIU/ml, luteinizing hormone (LH) levels of 68 mIU/ml, estradiol levels <20.00
ng/ml, triiodothyronine levels of 150.0 ng/dl, thyroxine (T4) levels of 8.0 ng/dl, thyroid-
stimulating hormone levels of 1.4 µIU/ml prolactin levels of 13.0 ng/ml, and a karyotype of
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Da Silva Rios et al.: A Case of Swyer Syndrome Associated with Advanced Gonadal
Dysgerminoma Involving Long Survival

46,XY. The patient was prescribed estrogens in combination with progestogens. A pelvic
ultrasound (US) was performed approximately 4 years later. This US revealed a mass with
irregular contours, heterogeneous echogenicity, and a largest diameter of 9.5 cm that in-
volved the uterus; this mass was interpreted as a solid pelvic tumor that required further
elucidation. The patient was subjected to a total hysterectomy and a bilateral salpingo-
oophorectomy. Perioperative observations revealed a rudimentary uterus, a nonadhered
and small left tube, a left gonad with a strip-like appearance, and a large irregular mass that
included the right adnexa and omentum. A histopathological examination revealed a right
adnexal tumor that measured 12 × 7 × 5 cm. This tumor had a shiny, lumpy surface and ex-
hibited an elastic consistency. Upon sectioning, multiple grayish nodules were observed;
certain nodules featured cystic cavities with yellowish-gold regions. A portion of the large
omentum that measured 18 cm along its longest axis had adhered to the tumor. A sample of
peritoneal fluid tested positive for malignancy. The histopathological report indicated that
the tumor was a stage 3 right-side adnexal dysgerminoma (fig. 1, fig. 2).
The patient was subsequently subjected to 12 sessions of chemotherapy. In a recent
routine visit, at the age of 47 years, the patient had no complaints. She reported that she had
been ingesting a daily dose of 0.625 mg of conjugated estrogens for the preceding 25 years
and told us that she did not wish to change this treatment because she had become well
adapted to it. Bone densitometry tests revealed osteopenia; no abnormalities were detected
by pelvic US, mammogram, or tumor marker tests.

Discussion

Individuals with Swyer syndrome exhibit female phenotypes and are typically raised as
girls; these individuals are generally diagnosed in adolescence when they seek medical assis-
tance for amenorrhea and the absence of secondary sex characteristics [5]. Her breasts were
consistent with the typical breast development among 11- to 15-year-old adolescents. Her
breasts were consistent with Tanner stage 4 [9]. Her vagina was normal and her cervix was
small; these characteristics are in accordance with the typical traits of Swyer syndrome pa-
tients [3].
Patients suspected to suffer from Swyer syndrome are first subjected to laboratory test-
ing for diagnostic confirmation. These tests include measurements of electrolytes and of the
hormones FSH, LH, prolactin, thyroid-stimulating hormone, free T4, sex hormone-binding
globulin, androstenedione, estradiol, and testosterone [1]. In the described case, FSH and LH
levels were elevated and estradiol levels were low; these findings are indicative of hy-
pogonadotropic hypogonadism, a condition consistent with descriptions of Swyer syndrome
in the extant literature. As a rule, Swyer syndrome patients exhibit low androgen levels and
low or undetectable levels of androgen precursors. Cytogenetic analyses of these patients
reveal a nonmosaic karyotype of 46,XY. In addition, patients can be tested for levels of anti-
Müllerian hormone and inhibin, although these tests are not mandatory [1].
Differential diagnoses of patients with primary amenorrhea should consider various
possibilities, including Mayer-Rokitansky-Küster-Hauser syndrome (XX), which is the sec-
ond most common cause of this condition; this syndrome is characterized by varying de-
grees of Müllerian duct abnormalities and a rudimentary or absent uterus [10]. In addition,
complete androgen insensitivity syndrome should be considered. Patients with this syn-
drome, which was formerly known as Morris syndrome, are XY individuals with primary
amenorrhea and normal breast and vaginal development, but with no uterus [11]. Karyotyp-
ing should be performed in any individual with elevated gonadotropins and pubertal delay.
 Case Rep Oncol 2015;8:179–184
DOI: 10.1159/000381451 © 2015 S. Karger AG, Basel 182
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Da Silva Rios et al.: A Case of Swyer Syndrome Associated with Advanced Gonadal
Dysgerminoma Involving Long Survival

Analyses of urinary steroid profiles are relevant when testosterone or cortisol deficiency is
suspected because these profiles allow these conditions to be distinguished from 5-alpha-
reductase deficiency. Once gonadal dysgenesis is confirmed, the tumor markers alpha-
fetoprotein, beta-human chorionic gonadotropin, lactate dehydrogenase, and alkaline phos-
phatase should be examined; however, according to certain authors, these markers should
only be measured in cases involving gonadal tumors [1]. Transabdominal US is the first-
choice diagnostic imaging method for investigating such lesions, with MRI restricted to cases
in which US fails to clearly reveal Müllerian structures or urinary tract abnormalities [1, 2].
In the case described in the current report, uterine contours, size, and echogenicity were not
clearly defined by the first US; thus, given that MRI was not available at our department at
that time, it could not be established whether the case involved myoma or an adnexal tumor.
Assessments of the NR5A1 gene are relevant for genetic counseling in cases with a relevant
family history [1]. In the present case, the family history was suggestive of Swyer syndrome
but did not provide conclusive evidence for this syndrome.
In cases of Swyer syndrome, after surgical treatment, hormone replacement therapy to
induce puberty and the development of secondary sex characteristics is indicated [4]. Estro-
gen therapy should be administered as quickly as possible to ensure adequate bone mass
formation and prevent reductions of bone mineral density that lead to osteopenia and oste-
oporosis. Cyclic estrogen and progesterone replacement is indicated until 50 years of age,
when hormonal therapy may be discontinued [1, 2]. In the case described in this report,
hormonal treatment commenced relatively late with respect to bone formation; this timing
could account for the appearance of osteopenia in the examined patient.
Patients with Swyer syndrome should be subjected to surgery for gonad removal as
soon as the diagnosis has been established because of their high risk for tumors such as dys-
germinomas, which are the most common type of tumor found among these patients [4]. The
objective of this surgery is to concurrently diagnose, stage, and treat the patient. For early-
stage patients, the recommended procedure is unilateral salpingo-oophorectomy because
this surgery preserves a patient’s fertility [8]. Unfortunately, in the case described in this
report, gonad removal surgery was performed only after a malignant tumor had progressed
to an advanced stage; thus, a hysterectomy was required. This hysterectomy requirement
represented a meaningful sacrifice for the patient; although the uterus of Swyer syndrome
patients is small [3], these women can become pregnant via egg donation. In fact, several
cases of pregnancy among Swyer syndrome patients have been described since 1988; the
prognoses for these pregnancies is similar to the prognoses for the pregnancies of 46,XX
patients with ovarian failure [12]. Adjuvant chemotherapy is particularly necessary in the
most advanced stages of disease. Dysgerminomas are highly sensitive to chemotherapy;
thus, the use of chemotherapy has been associated with a remarkable increase in patient
survival, particularly following the introduction of platinum-based regimens [8].
The survival rates of patients with XY gonadal dysgenesis and dysgerminoma are similar
to the survival rates of XX individuals with malignant ovarian germ cell tumors; in both types
of patients, survival rates are largely dependent on tumor stage [13]. In particular, survival
rates are lower among patients with more advanced tumors (stages 2–4; 53.9%) than among
patients with stage 1 tumors (96.9%) [13]. Reports regarding these patients largely reflect 5
years of follow-up but have seldom examined 10-year survival [14, 15]. The Swyer syn-
drome patient with advanced dysgerminoma who has been described in this report has ex-
hibited an extremely long survival time of 23 years, with no recurrence of disease.
In summary, the current case report is relevant because it calls attention to the need to
subject women with primary amenorrhea to thorough investigation to exclude Swyer syn-
drome and other chromosomal abnormalities associated with high rates of incidence of ma-
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DOI: 10.1159/000381451 © 2015 S. Karger AG, Basel 183
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Da Silva Rios et al.: A Case of Swyer Syndrome Associated with Advanced Gonadal
Dysgerminoma Involving Long Survival

lignant gonadal tumors. The accurate and early diagnosis of these abnormalities would allow
for conservative treatment, which can ensure the preservation of fertility, reduce emotional
trauma, and improve patient survival [1, 8].

Disclosure Statement

The authors declare that there is no conflict of interest regarding the publication of this
paper.

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Da Silva Rios et al.: A Case of Swyer Syndrome Associated with Advanced Gonadal
Dysgerminoma Involving Long Survival

Fig. 1. The dysgerminoma. Nests of tumor cells with a clear cytoplasm and well-defined membranes were
observed; fibrous septae and lymphocytic infiltrate were evident. × 100.

Fig. 2. a, b The dysgerminoma. Upon detailed examination, neoplastic cells with large nuclei, prominent
nucleoli and a clear cytoplasm were observed; mature lymphocytes were present amidst the fibrous
stroma. × 400.