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Aegean Journal of Obstetrics and Gynecology 3/3
Aegean Journal of Obstetrics and Gynecology
Case Report
Ovarian hilus cell hyperplasia and sertoli-leydig cell tumor in a patient with
postmenopausal virilization: a rare case report
Begüm Ertan a, , , Eyuphan Ozgozena, , Orkun Ilgen a, , Goksenil Bulbul b, , Baad Saa
a, , Cagnur Ulukus b,
a Department of Obstetrics and Gynecology, Dokuz Eylul University School of Medicine, Izmir, TURKEY
b Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, TURKEY
A B S T R A C T
Objective: We present a case report regarding a 71-year-old woman with postmenopausal virilization caused by ovarian hilus cell hyperplasia and Sertoli-Leydig cell
tumor(SLCT) who w as suf fered from hair loss, clitoromegaly and hirsutism.
Case Report: T a aa a a 351.24/dL . In the magnetic resonance imaging examination, a nodular formation of 20x26mm in size was
observed in the right ovary. At the transvaginal ultrasound, a cystic mass of 28x28mm was seen in the right ovary. Then we performed a total laparoscopic hysterectomy and
bilateral salpingo-oophorectomy. The final pathology showed a poorly differentiated SLCT at the right ovary and hilus cell hyperplasia at the left o vary. SLCTs, which are
relatively less common, are extremely rare to be seen in the postmenopausal period.
Conclusion: What distinguishes this case from others is that SLCT and hilus cell hyperplasia may cause virilization symptoms together, in addition to its prevalence in advanced
age.
Keywords: sertoli-leydig cell tumor; ovarian hilus cell hyperplasia; postmenopausal virilization; sex-cord-stromal tumors
A R T I C L E I N F O
Doi: 10.46328/aejog.v3i3.99
Article history:
Received: 29 August 2021
Revision received: 5 October 2021
Accepted: 9 November 2021
© 2021 AEJOG
Introduction
Virilization is a rare condition in postmenopausal hirsutism and is
associated with a high androgen level measured in the blood.
When such a clinic emerges, the first thing that should come to
mind is to rule out adrenal or ovarian malignancies. Although rare,
hilus cell tumors should also be considered [1]. Hilus cell
hyperplasia is a less common cause of this condition [2]. Sertoli-
Leydig cell tumors (SLCT), also knows as androblastoma, belong
to the category of sex cord-stromal tumors. SLCT of the ovary is
a significantly rare neoplasm accounting for <0.5% of all primary
ovarian neoplasms [3]. Although it is seen in any age group
between 2 and 75 years old, it is frequently seen in the 2nd - 3rd
decade. As it can be clinically asymptomatic, it may show clinical
differences in measurements ranging from severe virilizing
findings. Androgenic activity is observed in about half of the cases.
The tumor is often seen unilaterally and is diagnosed in 80% of
cases when they are at stage 1. The prognosis of SLCT is generally
promising, but it is closely related to the stage and grade of the
tumor. It is clinically malignant in approximately 10% of cases.
Pathologically, the presence of heterologous elements is
associated with a poor prognosis. Recurrence is usually within 2
years and occurs in the peritoneal cavity [4].
Corresponding author.
E-mail: begmertan@hotmail.com
OrcID: 0000-0002-0370-7509
The definition of anaplasia in cases with histologically moderate
change is associated with a poor prognosis and no other poor
prognosis criteria have been defined [5].
We present a rare case report of advanced age, postmenopausal
patient with hirsutism detected clinically and a mass in the ovary
determined by imaging methods, but later detected SLCT in the
right ovary and hilus cell hyperplasia in the left ovary.
Case Report
A 71-year-old female suffered from hair loss, clitoromegaly
and hirsutism started 5-6 months ago. The gravidity and parity
of the patient are G8P3. The patient has been in menopause
for 25 years and the first menstruation was at the age of 14.
T a a a a dc
period and there was no complaint of any hirsutism and
virilization. In the postmenopausal period, there was no
complaint other than mild-moderate hot flashes until the
virilization findings started 5-6 months ago. Other diseases of
the patient were hypothyroidism and adrenal adenoma. The
patient was performed from thyroid gland, laparotomic
cholecystectomy, and dilatation&curettage for 5 times. Due to
these new and sudden onset complaints, the patient was first
referred to the endocrinology outpatient clinic. During the
physical examination, hirsutism findings have occurred
especially under the chin, upper back, and around the chest.
Ferriman- Gallwey's score was 14 out of 36. Cliteromegaly was
detected in the pelvic examination.
Ean B, Ogo en O, Ilgen O, B lbl G, Saal B e al./ Aegean J O bstet Gynecol 3/3 page 83-86
84
Laboratory tests showed that the initial value of cortisol was
25.34 ug/dL, SHBG(sex hormone binding globulin) was 57.80
nmol/L, 1,4-Delta Androstenedione was 3.91 ng/mL,
ACTH(adrenocorticotropic hormone) was 18.10 pg/mL, total
testosterone was 351. 24 ng/dL, FSH(follicle-stimulating
hormone) was 35.44 mIU/mL, LH(luteinizing hormone) was
29.15 mIU/mL, estradiol was 54.30 pg/mL. Dexamethasone
suppression test was negative.
The endocrinologist noted that it is not compatible with the
clinical findings of the patient with Cushing syndrome, Conn
syndrome, or pheochromocytoma. The fecal occult blood test
was negative, either. Tumor markers(AFP(alpha fetoprotein),
CEA(carcinoembryonic antigen), CA(cancer antigen) 125, CA-
19-9 and CA15-3) were negative. At the MRI(magnetic
resonance imaging) scan, the uterus has an anteverted
appearance. An appearance compatible with uterine
leiomyoma with a size of approximately 2 cm was observed in
the left anterior inferior in the uterus. A nodular formation of
20x26mm in size was observed in the right ovary (Figure 1).
The left ovary was atrophic. At the transvaginal ultrasound,
the uterus is in large appearance. In the uterine fundal
section, an appearance compatible with the 2 cm myoma
uteri was observed. Endometrium was observed in normal
thickness. A cystic mass of 28x28mm was seen in the right
ovary. The left ovary was atrophic. We performed an
endometrial biopsy. The pathology resulted in an atrophic
endometrium. Then we performed a total laparoscopic
hysterectomy and bilateral salpingo-oophorectomy. The
frozen section found out SLCT at the right ovary. The final
pathology showed a poorly differentiated SLCT at the right
ovary and hilus cell hyperplasia at the left ovary. The tumor
was at stage IA of the 2014 classification of the International
Federation of Gynecology and Obstetrics (FIGO).
Figure 1: T2-weighted image (a) of the patient demonstrating
a low signal intensity mass (arrows) in the right ovary which
shows contrast enhancement on post-contrast fat saturated
T1-weighted image (b)
Surgical Specimen and Histopathology
Light microscopic examination of the right ovary revealed a
tumor was generally composed extensively of solid sheets of
poorly differentiated Sertoli cells -which may resemble a
fibrosarcoma, an undifferentiated carcinoma, or a primitive
germ cell tumor- with scattered clusters of Leydig cells.
Sertoli cells were in medium size, showed pleomorphism, had
scant cytoplasm, irregular nuclear membrane, and
inconspicuous or mild prominent nucleoli.
Immunohistochemically, in the right ovary, neoplastic cells
stained positive for calretinin, inhibin, CD56, WT-1, and
Melan-A (Figure 2); negative for MOC31, Pancytokeratin, and
EMA.
Figure 2: Immunohistochemical examination of right ovary,
poorly differentiated Sertoli Leydig Cell Tumor. (a) The
neoplastic cells are positive for calretinin (magnification
power: 20x). (b) The neoplastic cells are positive for inhibin
(magnification power: 20x). (c) The neoplastic cells are
positive for CD56 (magnification power: 20x). (d) The
neoplastic cells are positive for WT-1 (magnification power:
20x). (e) The neoplastic cells are focal positive for Melan-A
(magnification power: 20x).
In the left ovary, hilus cells also stained positive for calretinin,
inhibin, and Melan-A (Figure 3); negative for EMA. Based on
the histopathological and immunohistochemical findings; a
poorly differentiated SLCT in the right ovary and hilus cell
hyperplasia diagnoses in the left ovary were established.
Figure 3: Immunohistochemical examination of left ovary,
Hilus cell hyperplasia. (a) The hilus cells are immunoreactive
for calretinin (magnification power: 20x). (b) The hilus cells
are immunoreactive for inhibin (magnification power: 20x). (c)
The hilus cells are immunoreactive for Melan-A (magnification
power: 20x).
Discussion
SLCT is a rare ovarian cancer and it is seen more frequently
between the ages of 20-30 on average [5]. Macroscopically,
the size ranges from 2 to 35 cm and may be solid, solid-
cystic, or rarely cystic. It is mostly frequently encountered as
well and moderately differentiated tumors histologically [6].
In tumors with moderate differentiation, endodermal
elements are more frequently observed, and mesenchymal
structures are more frequently observed in association with
poorly differentiated tumors. The prognosis of SLCT is
generally promising, but stage and level of differentiation are
significantly associated with prognosis and recurrence [7].
The clinically malignant tumors were detected in %19 of the
tumors with heterologous elements in a study by Young and
Scully [7]. Adjuvant chemotherapy is recommended for
patients with advanced-stage, intermediate and poor
differentiation, retiform pattern, and presence of
heterologous elements [8]. Many studies show that SLCTs
can be seen in every decade of life, especially in the second
and third decades [4,8]. However, the age of clinical
a ca a 71. Accd D a.
conducted with 17 patients, 5 patients (29.4%) had an
androgenic clinic. (oligomenorrhea, amenorrhea, hirsutism,
clitoromegaly) 6 patients (35.3%) had estrogenic manifesto
(postmenopausal bleeding, menometrorrhagia) and 6 patients
(35.3%) non-hormonal manifestation (abdominal pain,
abdominal distension). In our case, our patient had an
androgenic clinic and had no post-menopausal bleeding or
other non-hormonal findings [9].
85
Rutgers and Scully et al. have described hilus cell hyperplasia
in bands adjacent to ovarian cysts or tumors. More than half
of these identified patients were accompanied by virilization
symptoms [7]. Also, the relationship between hilus cell
hyperplasia and virilization is not clear. In affected patients,
oophorectomy improves androgen excess, alternative
therapies have been reported and oophorectomy is not the
only treatment method. AFP is a glycoprotein detected at low
levels in the blood of healthy adult patients. It is the main
source of the yolk sac and liver production during the fetal
period. AFP levels above normal in adulthood may be
evidence of hepatocarcinoma and germ cell tumors.
Moreover, it may suggest an ovarian or testicular tumor. This
glycoprotein has already been studied extensively as a tumor
marker and is routinely used both in diagnosis and in follow-
up.
Schneider et al. found ovarian SLCT with a high level of AFP
secretion in some patients [10].
According to the study of Sigismondi et al., AFP values were
measured in 13 patients SLCT group, and AFP values were
found high in 3 patients [11]. According to the study
conducted by Castro et al., which included 12 SLCT patients,
increased levels of AFP were measured in 5 patients.
Moreover, a more advanced stage and a more difficult
treatment were encountered in these patients at the time of
diagnosis. In our case report, CEA, CA125, CA 19-9, CA 15-3
were normal, including AFP. SLCT treatment is still a
controversial subject because our knowledge about this
disease is limited and the factors affecting the prognosis of
the patient are not known exactly. According to Colombo et
al., surgery is the standard and primary approach for this
disease [12]. Because many SLCT cases are unilateral and
limited to the ovary. Unilateral salpingo-oophorectomy and
staging is an adequate treatment for these patients in cases
where there is no extra ovarian disease and who want the
preservation of fertility. Many authors emphasize that
endometrial evaluation is particularly important in these
patients due to concomitant endometrial neoplasia. According
to the study by Colombo et al., in cases of more advanced
disease or bilateral tumors, hysterectomy and bilateral
salpingo-oophorectomy and meticulous surgical staging are
required in postmenopausal women [12]. Moreover, the
examination of the abdominal cavity, cytological sampling
from intraabdominal free fluid, peritoneal biopsy,
omentectomy, and pelvic-paraaortic lymph node dissection
are recommended. However, the place of surgical staging is
controversial, and the benefits of a detailed surgical staging
should be considered in addition to the severe morbidity it
creates. Brown et al. emphasized that lymphadenectomy may
be neglected in order not to increase the potential surgical
risk, since lymph node metastasis appears very rarely in sex-
cord stromal tumor patients [13]. In our patient, we
performed a total laparoscopic hysterectomy and bilateral
salpingo-oophorectomy with frozen pathology. The frozen
pathology result was found as a SLCT at the right ovary and
the left ovary showed no malignancy. The abdominal cavity
was examined and no abnormality was found. Peritoneal
biopsy and lymph node sampling were not performed to avoid
additional surgical morbidity to the patient. No complications
were encountered during the inpatient follow-up. Blood test
after 5 days after the surgery was cortisol 12.08 ug/dL, total
testosterone <7.00 ng/mL, DHEA-
SO4(dehydroepiandrosterone-sulfate) 28.05 ug/dL. The
patient remains under surveillance.
In the study performed by Colombo et al., it was stated that
adjuvant chemotherapy should be given in poorly
differentiated SLCTs, heterologous elements containing
SLCTs, and advanced-stage patients [12]. In the study
conducted by Castro et al., adjuvant therapy was applied to
2 out of 12 patients and the tumors were poorly and
moderately differentiated. Recurrence was not observed in any
patient [14]. In the study conducted by Schneider et al., only
1 patient received adjuvant therapy in 24 stage 1A patients
(including moderate and poor differentiation), and no
recurrence was observed in any patient [10]. However, to
understand the correct indication of adjuvant therapy, we need
to understand the prognostic factors that affect this disease.
And, randomized controlled trials should be designed in these
SLCT patients. The main reason for this limitation is that this
disease is very rare, occurs in a wide age range, and appears
in different stages. In our case, adjuvant therapy was not
considered for the patient. It was planned to follow the patient
clinically and radiologically.
SLCT is generally a disease with a good prognosis. Moreover,
since adjuvant therapy may come the next day, examining
heterologous elements and searching for the presence of
anaplasia is of critical importance for these patients.
Also, the follow-up of these patients is very important to detect
and intervene in the early stage of recurrence.
With this case report, we see that SLCT is a condition that can
be encountered in elderly patients.
We believe that case reports of such rare cases will help us
take our current knowledge to the next level. Thanks to more
reporting of such rare diseases, they will have a positive
contribution to the completion of our missing information.
Statement of ethics: This report followed guidelines to be
HIPAA compliant and permission was obtained from the patient
to publish identifiable photographs. The study adhered to the
tenets of the Declaration of Helsinki.
Acknowledgments: We would like to thank Dr. Tevfik Demir(
University of Dokuz Eylul) and Dr. Mustafa Secil ( University of
Dokuz Eylul) for comments on the manuscript. The authors
declare that they have no conflicts of interest.
Disclosure
Authors have no potential conflicts of interest to disclose.
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