Original Study

Evaluation and Treatment Results of Ovarian Cysts in Childhood

and Adolescence: A Multicenter, Retrospective Study of 100
Patients
Banu Kucukemre Aydin MD 1,*, Nurcin Saka MD 1, Firdevs Bas MD 1, Yasin Yilmaz MD 1,
Belma Haliloglu MD 2, Tulay Guran MD 2, Serap Turan MD 2, Abdullah Bereket MD 2,
Gul Yesiltepe Mutlu MD 3, Filiz Cizmecioglu MD 3, Sukru Hatun MD 3, Digdem Bezen MD 4,
Filiz Tutunculer MD 4, Nurcan Cebeci MD 5, Pinar Isguven MD 6, Nihal Memioglu MD 7, Oya Ercan MD 8,
Sukran Poyrazoglu MD 1, Ru € veyde Bundak MD 1, Feyza Darendeliler MD 1
1
Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Istanbul, Turkey
2
Marmara University, Medical Faculty, Department of Pediatrics, Pediatric Endocrinology Unit, Istanbul, Turkey
3
Kocaeli University, Medical Faculty, Department of Pediatrics, Pediatric Endocrinology Unit, Kocaeli, Turkey
4
Trakya University, Medical Faculty, Department of Pediatrics, Pediatric Endocrinology Unit, Edirne, Turkey
5
Derince Training and Research Hospital, Department of Pediatrics, Kocaeli, Turkey
6
Sakarya University, Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Sakarya, Turkey
7
American Hospital, Department of Pediatrics, Istanbul, Turkey
8
Istanbul University, Cerrahpasa Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Istanbul, Turkey

a b s t r a c t
Study Objective: To investigate the characteristics of children with ovarian cysts and evaluate treatment strategies.
Design: Retrospective study.
Setting: Eight pediatric endocrinology clinics, Turkey.
Participants: A total of 100 children and adolescents with ovarian cysts.
Interventions: Patient data collected via retrospective chart review. Patients were stratified according to age into 4 groups (newborns,
1-12 months, 1-8 years, and 8-18 years).
Main Outcome Measures: Special emphasis was given to torsion and tumor cases, concomitant diseases, treatment modalities, and
problems during follow-up.
Results: Most newborns and infants were asymptomatic with the cysts being discovered incidentally; in girls ages 1-8, symptoms were
common, including breast budding (47.1%, 16 of 34) and vaginal bleeding (29.4%, 10 of 34). Girls older than 8 years mostly presented with
abdominal pain (31.6%, 12 of 38) and menstrual irregularity (21.1%, 8 of 38). Most of our patients were diagnosed with a simple
ovarian cyst, but 9 patients were found to have ovarian tumors. Ovarian torsion was detected in 7 patients; 5 with large and 2 with small
cysts (!20 mm). Two patients had central precocious puberty (CPP) at presentation and 5 patients developed CPP during follow-up.
The surgical intervention rate was high (38%, 38 of 100), but was associated with earlier treatment year, and this association remained
significant after adjusting for confounders (P 5 .035).
Conclusion: Most girls have simple cysts, which have a favorable prognosis without intervention; however, there might be coexisting
pathologies or complications such as tumors, torsion, and CPP; hence these patients should be evaluated accordingly and treated with a
multidisciplinary approach.
Key Words: Ovarian cyst, Ovarian tumor, Ovarian torsion, Precocious puberty, Aromatase inhibitors

Introduction (USG), but the prevalence of clinically significant ovarian

Adnexal masses are uncommon during childhood, but
their recognition is increasing perhaps as a result of the
increasing availability of advanced diagnostic technologies.
Finding a mass in a child always raises concern for
malignancy, but the most adnexal masses in children are
thought to be benign ovarian cysts.1 Up to 98% of female
newborns have small ovarian cysts on ultrasonography
The authors indicate no conflicts of interest.
* Address correspondence to: Banu Kucukemre Aydin, MD, Istanbul Universitesi,
Istanbul Tip Fakultesi, Cocuk Sagligi ve Hastaliklari AD, Capa, Fatih, Istanbul 34093,
Turkey; Phone: þ90 212 414 20 00/33284
E-mail address: bkucukemre@yahoo.com (B.K. Aydin).
1083-3188/$ - see front matter Ó 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.jpag.2017.01.011
cysts in this age group is approximately 1 in 2500 live
births. In contrast, ovarian cysts are identified in 2%-3% of
girls aged younger than 8 years of age when USG is
performed for other reasons.2 Benign and malignant tumors
of the ovary, tubo-ovarian abscess (TOA), genitourinary
anomalies, and ectopic pregnancy are other diagnoses to be
excluded.1 Ovarian neoplasms are very rare in children but
should be considered in the differential diagnosis especially
with complex cysts. Germ-cell tumors are the most
common ovarian neoplasm in childhood and adolescence
with mature cystic teratomas accounting for 55%-70% of
cases.3 These tumors embrace tissues from at least 2 germ
layers and can form skin derivatives, teeth, hair, cartilage,
450 B.K. Aydin et al. / J Pediatr Adolesc Gynecol 30 (2017) 449e455
neural elements, fat, and bone. Juvenile granulosa cell
tumors (JGCTs) are malignant stromal tumors that present
in childhood, adolescence, and young adulthood with
symptoms (such as breast budding, vaginal bleeding, and
menstrual irregularity) due to estradiol (E2) production.3
The diagnosis of McCune-Albright syndrome (MAS)
should be considered if there is evidence for peripheral
precocious puberty (PPP), polyostotic fibrous dysplasia, and
 au lait pigmentation.4 This disorder, with highly
cafe
variable clinical features, is caused by the postzygotic
activating mutation of the GNAS1 gene, which encodes the
a-subunit of the stimulatory G protein.5 This mutation leads
to ligand-independent activation of cyclic adenosine
monophosphate signaling.6 PPP is the most common
endocrinological manifestation of MAS in girls, and is
caused by estrogen-producing functional ovarian cysts
(FOC).7
Previous studies in children with ovarian cyst were
predominantly from surgery clinics. Most studies have
focused on surgical indications and techniques, and lack
long-term clinical follow-up. In this article, we report on a
retrospective comprehensive evaluation of 100 children
with ovarian cysts. We gave special emphasis to torsion and
tumor cases, concomitant diseases, treatment modalities,
and problems during follow-up.
Materials and Methods
This was a multicenter retrospective study of 100 girls
with ovarian cysts who received medical care at 8 pediatric
endocrinology clinics in the Marmara Region of Turkey
between June 1994 and October 2013. Data were derived
from the paper patient charts using a structured review of
medical records in which patient's age, symptoms at
presentation, serum gonadotropin and E2 levels, size and
ultrasonographic features of the cyst, treatment modalities,
final diagnosis, follow-up time, and problems during follow
up-were recorded. Participating centers were asked to
review medical records of all patients diagnosed with
ovarian cyst. A total of 105 study forms were completed and
sent to the principal investigator (N.S.). Four patients were
excluded because they had cysts less than 10 mm and 1
patient, with dysgerminoma in 1 gonad and gonado-
blastoma in the other, because of her 46,XY karyotype.
Patients with ovarian tumors were included, if their initial
diagnosis was ovarian cyst.
The study population was stratified into 4 groups on
the basis of patient age: group 1 included antenatal
and newborn patients, group 2 included patients age
1-12 months (infants), group 3 included patients
age 1-8 years (prepubertal ages), and group 4, patients age
8-18 years. The cysts were classified according to size and
ultrasonographic features. Cysts with a diameter between
10 and 20 mm were defined as small cysts, between 20 and
40 mm as medium-sized, and greater than 40 mm were
defined as large cysts. Anechoic, homogeneous, thin-walled,
unilocular and unilaterally located cysts were defined as
simple. Complex cysts were defined as those with thick
walls with a solid structure and septa, and containing blood
clot and debris.8
Treatment modalities were investigated by using a cutoff
date (before/after 2010). Our rationales for this cutoff date
were: (1) almost all studies of pediatric ovarian cysts have
been published after 2005 (approximately 80% in PubMed),
and increased awareness of ovarian-sparing procedures for
children and adolescents; and (2) balanced distribution of
our study group before and after this time point (47 vs 53
patients).
Statistical analysis was done with SPSS 15.0 software
(SPSS Inc, Chicago, IL). Univariate analysis was performed
using the Mann-Whitney U and Kruskal-Wallis tests for
comparison of continuous variables and the c2 test for
comparison of percentages. Linear regression was done to
evaluate the association between treatment year
(before/after 2010) and application of ovarian-sparing
procedures. A multiple linear regression model was built
to adjust for differences in baseline characteristics. Data are
presented as the mean  SD of the mean and a P value of
less than .05 is considered significant.
The Istanbul University review board approved the
study.
Results
The mean age at diagnosis was 6.9  5.7 years (range,
0-17.9 years). Eighteen patients were diagnosed during the
antenatal or newborn period (group 1), 10 in infancy (group
2), 34 at ages 1-8 years (group 3), and 38 patients were
identified after the age of 8 years (group 4).
The symptoms at presentation were significantly
different among the 4 groups (P ! .001; Table 1). Most
newborns and infants were asymptomatic with the cysts
being discovered incidentally, in girls ages 1-8 years, the
most common symptoms were breast budding (47.1%, 16 of
34) and vaginal bleeding (29.4%, 10 of 34). Patients older
than 8 years most often presented with abdominal pain
(31.6%, 12 of 38) or menstrual irregularity (21.1%, 8 of 38).
There was a significant difference between the
maximum cyst diameters among patients in the 4 groups
(P 5 .003; Table 2), but when cysts were viewed as simple or
complex using USG, there was no significant difference
among the age groups (P 5 .72; Table 2). Mean luteinizing
hormone (LH) and follicle-stimulating hormone (FSH)
levels were significantly higher in group 4 (P ! .001 and
P ! .001, respectively), whereas mean E2 levels were
highest in group 3 (P 5 .025; Table 1).
Ovarian Torsion
Ovarian torsion was detected in 7 patients (7%); 4 in
group 3 and 3 in group 4. There were no reported cases of
torsion in groups 1 or 2 (Table 1). All of the patients with
torsion presented with abdominal pain. Most of the cysts in
patients with torsion were classified as large (71.4%, 5 of 7),
but there were 2 patients with small cysts, and no
significant difference was found between the cyst
diameters of the children with or without torsion
(49.4  24.2 mm vs 40.8  24.8 mm, respectively, P 5 .28).
Age at diagnosis, gonadotropin, and E2 levels as well as
ultrasonographic features of the cysts were not different
 B.K. Aydin et al. / J Pediatr Adolesc Gynecol 30 (2017) 449e455 451

Table 1
Clinical and Laboratory Characteristics According to Patient's Age

Characteristics Group 1 (n 5 18) Group 2 (n 5 10) Group 3 (n 5 34) Group 4 (n 5 38) P

Age at diagnosis, years 0.0  0.0 0.47  0.21 5.5  1.9 13.1  2.7 ! .001
Symptoms, n (%) ! .001
Incidental finding 15 (83.2) 6 (60) 1 (2.9) 11 (28.9)
Abdominal pain e e 7 (20.6) 12 (31.6)
Breast budding 1 (5.6) 2 (20) 16 (47.1) e
Vaginal bleeding e 1 (10) 10 (29.4) 3 (7.9)
Abdominal swelling e 1 (10) e 1 (2.6)
Menstrual irregularity e e e 8 (21.1)
Hirsutism e e e 3 (7.9)
Labial hyperpigmentation 1 (5.6) e e e
Ambiguous genitalia 1 (5.6) e e e
Ovarian torsion, n (%) e e 4 (11.8) 3 (7.9) .34
LH, mIU/mL 0.30  0.50 0.17  0.21 0.09  0.04 4.3  3.9 ! .001
FSH, mIU/mL 3.37  2.41 3.18  2.00 1.06  1.51 4.8  2.7 ! .001
Estradiol, pg/mL 26.8  21.3 16.6  6.3 144.4  311.9 63.4  54.2 .025

FSH, follicle-stimulating hormone; LH, luteinizing hormone

All values are mean  SD, except if otherwise stated. Group 1 includes newborns, group 2, infants (1-12 months), group 3, children aged 1-8 years, and group 4, children and
adolescents aged 8-18 years.
Statistically significant P-values are indicated in bold.

between the patients with or without torsion (data not
shown). Patients with ovarian torsion were diagnosed with
simple cysts (n 5 6; 85.7%) and mature teratoma (n 5 1).
Five patients were treated with oophorectomy and 2
patients with cystectomy.
Ovarian Tumors
Most of the study population had simple cysts, but 5
patients were diagnosed with mature teratoma and 4 with
JGCTs. The clinical and laboratory findings in patients
with ovarian tumors are shown in Table 3. There was no
significant difference between the ages, symptoms at
presentation, or LH, FSH, or E2 levels of the patients with or
without ovarian tumor (data not shown). All of the tumor
patients presented to the clinic with a symptom; none were
diagnosed incidentally. The youngest patient with a tumor
was 0.3 years old, and the oldest was 15.5 years old. Mean
cyst diameter was 38.7 (22.2) mm in patients with simple
cysts, and 71.0 (32.9) mm in patients with ovarian tumors
(P 5 .01). Most of the tumors were less than 40 mm on USG,
but cyst diameters were 20-40 mm in 3 patients with
teratoma. All of the patients with ovarian tumor had
complex cysts on USG.

Table 2
Cyst Characteristics, Initial Treatment, Diagnosis and Problems During Follow-up

Characteristics Group 1 (n 5 18) Group 2 (n 5 10) Group 3 (n 5 34) Group 4 (n 5 38) P

Cyst ultrasonographic features, n (%) .72

Simple 3 (16.7) 4 (40) 17 (50) 20 (52.6)
Complex 5 (27.8) 2 (20) 13 (38.2) 17 (44.7)
Not known 10 (55.6) 4 (40) 4 (11.8) 1 (2.6)
Cyst diameter (mm) 54.0  26.4 19.8  1.49 42.3  26.8 41.4  21.6 .003
Cyst diameter groups, n (%) .001
10-20 mm 1 (5.6) 6 (60) 9 (26.5) 3 (7.9)
20-40 mm 4 (22.2) 4 (40) 8 (23.5) 16 (42.1)
O40 mm 10 (55.6) e 16 (47.1) 18 (47.4)
Not known 3 (16.7) e 1 (2.9) 1 (2.6)
Initial treatment, n (%) .042
Spontaneous regression 6 (33.3) 9 (90) 17 (50) 23 (6.5)
Oophorectomy 8 (44.4) 1 (10) 9 (26.5) 3 (7.9)
Cystectomy 4 (22.2) e 4 (11.8) 9 (23.7)
Aromatase inhibitor e e 4 (11.8) e
GnRH agonist e e e 2 (5.3)
Oral contraceptive e e e 1 (2.6)
Diagnosis, n (%) .54
Simple cyst 18 (100) 9 (90) 29 (85.3) 35 (92.1)
Mature teratoma e 1 (10) 3 (8.8) 1 (2.6)
Juvenile granulosa cell tumor e e 2 (5.9) 2 (5.3)
Follow-up time, years 2.6  2.8 2.67  4.48 2.9  3.1 1.0  .9 .06
Problems during follow-up, n (%) .18
None 6 (33.3) 4 (40) 21 (61.8) 23 (60.5)
Recurrent cysts e 1 (10) 3 (8.8) 4 (10.5)
Central precocious puberty 2 (11.1) 1 (10) 2 (5.9) e
No follow-up data 10 (55.6) 4 (40) 8 (23.5) 11 (29)

GnRH, gonadotropin releasing hormone

All values are mean  SD, except if otherwise stated. Group 1 includes newborns, group 2, infants (1-12 months), group 3, children aged 1-8 years, and group 4, children and
adolescents aged 8-18 years.
Statistically significant P-values are indicated in bold.
452 B.K. Aydin et al. / J Pediatr Adolesc Gynecol 30 (2017) 449e455

Initial Treatment

Central precocious puberty

Treatment modalities were significantly different
Problems during

Tubo-ovarian abscess
among the 4 groups (P 5 .042); most of the patients in
Follow-up

No follow-up data
group 1 underwent oophorectomy, but in the other 3
groups most cysts regressed spontaneously (Table 2). Five
of the 7 patients with torsion had oophorectomy and in 2
None
None
None
None
None
None
the cyst was excised selectively. All patients with ovarian
tumors were treated with surgical modalities such as
Concomitant Diseases

oophorectomy and cyst removal (n 5 6 and n 5 3,

Congenital adrenal
respectively). After 2010, patients were more likely to be

hyperplasia
treated with ovarian-sparing procedures compared with
earlier years (90.6% (48 of 53) vs 65.9% (31 of 47);
Epilepsy

P 5 .035), and the association remained significant

No
No
No
No
No
No

No

after adjusting for patient's age, symptoms, cyst size,

ultrasonographic features, occurrence of torsion, and
Oophorectomy
Oophorectomy
Oophorectomy
Oophorectomy

Oophorectomy
Oophorectomy

diagnosis (P 5 .035).
Treatment

Cystectomy

Cystectomy
Cystectomy

Pharmacologic treatment was used in 7 patients.

Aromatase inhibitors (AIs) were the treatment in 4
patients with symptoms due to high E2 levels.
Gonadotropin levels were suppressed and E2 levels were
Torsion

elevated in accordance with PPP in those patients.

Yes
No

No
No
No
No
No
No
No

Gonadotropin-releasing hormone analogue therapy was

Cyst USG

administered in 2 patients diagnosed with idiopathic

Complex
Complex
Complex
Complex
Complex
Complex
Complex
Complex
Complex
Features

central precocious puberty (CPP) and ovarian cyst

simultaneously. These patients presented with vaginal
bleeding at the ages of 8.3 and 9.8 years, and their basal
Cyst Diameter,

gonadotropin levels were high. In 1 post pubertal patient

mm

35
60
110
35
110

97
82
39
e

with a 55-mm simple cyst and menstrual irregularity, an

FSH, follicle stimulating hormone; JGCT, juvenile granulosa cell tumor; LH, luteinizing hormone; USG, ultrasonography

ethinyl E2-drospirenone combination was used.

Estradiol,

Problems During Follow-up and Concomitant Diseases

pg/mL

8.0

20.0
20.0
170.0
22.0
135.1
54
e

Mean follow-up time and problems during follow-up

were not significantly different among the 4 groups
mIU/
FSH,

(P 5 .06 and P 5 .18, respectively; Table 2). Most patients

mL

1.8
1.5
2.0
2.3
1.0
6.8
1.4
e

did not experience any problem during follow-up, but 8

patients had recurrent cysts and 5 patients developed CPP
mIU/
LH,

mL

0.2

0.2
0.1

0.3
1.8

(Table 2). There were no follow-up data available in 33

e

children (33%).
A complex cyst with a maximum diameter of 39 mm
Menstrual irregularity
Abdominal swelling
Clinical and Laboratory Characteristics of Patients with Ovarian Tumor

was found in an USG evaluation being performed for

Vaginal bleeding
Symptoms

Abdominal pain

Abdominal pain

Abdominal pain

Abdominal pain

abdominal pain in a 15.5-year-old adolescent who

Breast budding

Breast budding

was receiving hydrocortisone and fludrocortisone

replacement for salt wasting congenital adrenal
hyperplasia (CAH) due to 21-hydroxylase deficiency
(21-OHD). Cystectomy and histopathological examination
Age at Diagnosis,

revealed the diagnosis of mature teratoma in this patient

(Table 3). Two and a half years after her cystectomy, she
years

0.3

3.3

6.2

13.6
15.5

was found to have a recurrent cyst and diagnosed with

2

7
11

TOA. She had also undergone genital tract surgery for

external genitalia virilization of CAH in infancy.
One patient presented with vaginal bleeding and cafe 
Histopathologic Diagnosis

au lait spots when she was 9 months old and diagnosed

with MAS. During follow-up, she was treated with AIs and
teratoma
teratoma

teratoma
teratoma

teratoma

fibrous dysplasia was added to her symptoms.

A 5.5-year-old girl presented to clinic with vaginal
bleeding and experienced many recurrent FOC during
Mature
Mature

Mature
Mature

Mature
Table 3

JGCT

JGCT
JGCT
JGCT

2.3 years of follow up and treated with AIs. She did not
have other features of MAS. Her genetic analysis from a
 B.K. Aydin et al. / J Pediatr Adolesc Gynecol 30 (2017) 449e455
blood sample was normal, but because MAS is a mosaic
disease and the mutations are often found in affected
tissues we could not rule out the diagnosis.
Two postpubertal patients with recurrent cysts
and menstrual irregularity were treated with an
E2-drospirenone combination. In the remaining 3 patients
recurrent cysts regressed spontaneously.
Three of the 5 patients who developed CPP during the
follow-up interval had been treated with oophorectomy
with an initial diagnoses of mature teratoma (n 5 1) and
simple cysts (n 5 2). One patient presented with apparent
PPP, and developed CPP during the follow-up. The last
patient had been diagnosed antenatally with no
obvious clinical disorder and the cyst had regressed
spontaneously. There was no other evident cause for CPP
in those 5 girls.
A newborn presented with ambiguous genitalia and an
abdominal mass, and was diagnosed with salt wasting
CAH due to 21-OHD; an abdominal USG examination
revealed a large, unilocular right ovarian cyst measuring
100  80  70 mm. After initiation of hydrocortisone and
fludrocortisone treatment, the cyst was surgically excised
and histopathology revealed a follicular cyst. Details of this
case were reported elsewhere.9
Discussion
Etiology and clinical characteristics of ovarian cysts in
children differ on the basis of age and pubertal status, and
accordingly, we divided our patients into 4 age groups. In
the antenatal period, maternal and placental hormones as
well as fetal gonadotropins might stimulate the ovaries2
and after birth some cysts resolve spontaneously whereas
some cysts might continue to enlarge perhaps because of
high gonadotropin levels during minipuberty.8 For most of
our patients with neonatal cysts, the cysts were detected
with prenatal USG without any complaints, and despite no
documented torsion or tumor, the surgery rate in this group
was very high. There was no standardized management
protocol identified in the participating centers, and cysts
were managed according to surgeons' judgment and
preference. We believe that the high surgical intervention
rate was partly because of the concerns over potential
complications because larger cysts are known to be more
prone to torsion and spontaneous bleeding, and mean cyst
diameter was highest in our newborn patients. Moreover,
the relatively shallow pelvis of the newborn was suggested
to increase the risk of torsion.2,8 Furthermore, most of the
patients in this group (61%, 11 of 18) were treated before
2010. Treatment of ovarian cysts has become less invasive,
with the aim of sparing ovarian tissue by follow-up without
intervention, or with the use of ovary-preserving surgeries
even in patients with torsion. However, before this decade,
oophorectomies were performed more commonly in
pediatric patients.10,11 It was believed that unilateral
oophorectomy does not affect ovarian reserve, but studies
have reported an association between unilateral
oophorectomy and higher FSH levels at age 35-39 years
with increased risk for early menopause.12,13 Currently, the
recommendation is to preserve the ovary unless the
453
pathology is likely to be malignant.10 Similar to our results,
Papic et al14 reported a decreased surgery rate from 83% in
1997-2001 to 64% in 2009-2012. Hernon et al11 reported
58% oophorectomy rate in 155 children and adolescents
who presented to a children's hospital with ovarian cysts
from 1991 to 2007 of which 83% were reported to have
benign or normal histopathology. They called for a more
multidisciplinary approach in an effort to increase the level
of conservative management.
Ovarian cysts are least common in prepubertal girls
because of low gonadotropin and sex hormone levels.2 Most
of our patients aged 1-8 years presented with the
symptoms of autonomous estrogen production, and in
accordance with their symptoms, their E2 levels were
higher and gonadotropin levels were lower. In addition to
PPP cases, there were 2 girls with CPP at presentation, and
an additional 5 girls developed CPP during the follow-up.
CPP is usually associated with multiple, small ovarian
cysts, but large ovarian cysts have also been reported.15
Elevated basal LH and FSH levels suggested CPP in
patients whose cysts and symptoms regressed with
gonadotropin-releasing hormone analogue therapy. One of
our patients presented with apparent PPP, but developed
CPP during the follow-up. High sex hormone levels due to
FOC might trigger CPP, presumably due to early maturation
of the hypothalamic-pituitary-gonadal axis.16 Three of the 5
patients who developed CPP during the follow-up had no
history of PPP, but had been treated with oophorectomy in
younger ages (2 in infancy). Because this was a retrospective
study with a small number of CPP cases, we cannot claim an
association between oophorectomy and CPP; it might
simply be a coincidence. It is interesting to speculate,
however, that because of loss of 1 ovary, there is a
compensatory increase in gonadotropin levels, and this
association should be evaluated in larger series.
AIs have been used to treat hyperestrogenism, hyper-
androgenism, pubertal gynecomastia, and short stature
and/or delayed puberty in children,17 but there has been no
prospective randomized controlled study or large case
series of AI therapy in girls with isolated FOC. In our small
group of patients, AIs seemed to alleviate the bothersome
symptoms in 4 girls with isolated FOC, and long-term AI
therapy was used without any side effects in 2 patients
(with MAS and suspected MAS), but for recommendation of
such a controversial therapy for FOC in children, prospective
randomized controlled trials with long term follow-up are
needed.
Most ovarian tumors in children are solid on USG or
computerized tomography imaging, but might have cystic
components. JGCTs, mixed germ-cell tumors, and benign or
malign teratomas might rarely present like an ovarian cyst.2
Most of our patients had simple cysts, which regressed
spontaneously without any complication, but there were 5
teratomas and 4 JGCTs. In girls who presented with the
symptoms of autonomous estrogen production, JGCT is an
important differential diagnosis because 70% of all girls
with this tumor were reported to have similar clinical
findings and approximately 85% similar laboratory
findings.18,19 Accordingly, 3 of the 4 patients with JGCT
presented with symptoms due to high E2 levels in our
454 B.K. Aydin et al. / J Pediatr Adolesc Gynecol 30 (2017) 449e455
study. Previous studies in children and adolescents mostly
focused on patients who received surgical treatment for
ovarian masses. Even in these studies, most of the children
were diagnosed with benign lesions.20e25
Suggested mechanisms for ovarian cysts in adolescence
are anovulation with persistence of the remaining follicle,
and persistence of the corpus luteum.2 In our pubertal
patients, abdominal pain and menstrual irregularity were
the most common symptoms. Similar to our findings,
Kanizsai et al26 reported that irregular menstrual cycles was
the most common presenting symptom, followed by
abdominal pain and a palpable mass. FOC can cause
menstrual irregularities in adolescents.3 More than 90% of
follicular and corpus luteum cysts resolve spontaneously,2
and hormonal treatment was not shown to hasten
regression but might be recommended in pubertal girls
who have menstrual irregularity that contributes to cyst
formation from unopposed estrogen stimulation.3 In
agreement with previous studies, most of the cysts in this
patient group regressed spontaneously.
Ovarian torsion is a rare but serious complication of
ovarian masses. Late diagnosis can cause loss of an ovary,
peritonitis, and even death. Torsion was detected in 7
patients in our population, and all of them presented with
abdominal pain. None of the patients developed torsion
while waiting for spontaneous cyst resolution. Most of the
cysts with torsion were large, but cyst diameter was less
than 20 mm in our 2 prepubertal patients with ovarian
torsion. Ashwal et al27 reported ovarian torsion with
normal-appearing ovaries on abdominal ultrasound in 71%
of their premenarcheal patients. Suggested mechanisms in
those cases were presence of an abnormally long tube,
mesosalpinx, mesovarium, or adnexal venous congestion
due to premenstrual hormone activity or jarring
movements of the body. Shah et al28 reported that early
polycystic ovary syndrome might be an underlying cause of
unexplained ovarian torsion in children. Most of our
patients with torsion had simple cysts, but there was 1
patient with mature teratoma. In patients with torsion, the
rate of malignancy was very low, approximately 2%, and
adhesions with surrounding tissues was suggested as a
mechanism.29
We chose 10 mm as the lowest cutoff limit for the
definition of an ovarian cyst because of the symptoms and
complications in relatively small cysts (10-20 mm) in our
study population. Most previous studies used a cutoff limit
of 20 mm, which might be appropriate for neonatal,
pubertal, and postpubertal cases, but we believe that cysts
larger than 10 mm could be clinically important, especially
in prepubertal girls. In addition to our observations, King
et al30 reported that ovarian cysts greater than 9 mm in
diameter are an indicator of autonomous ovarian activation
in this age group.
There are a few case reports of patients with CAH who
developed ovarian cysts.31,32 Our series includes 2 such
patients. Wakakuri et al33 reported a giant ovarian cyst in a
poorly controlled patient with simple virilizing 21-OHD,
and regression of the cyst with appropriate steroid
treatment. Ovarian microcysts are common in patients with
nonclassical CAH,34 in whom disruptions of gonadotropin
secretion by adrenal androgen excess as well as a direct
effect on the ovaries were suggested mechanisms.31,35,36
Weil et al37 showed that androgens might increase
follicular FSH receptors and promote follicular growth in
rhesus monkeys. Anderson et al38 reported an increase in
follicular cystic fluid to very high levels concurrent with the
development of follicular cysts in immature female rats
after dehydroepiandrosterone treatment. One of our
patients with CAH was diagnosed with a mature teratoma.
Although there are a few case reports of androgen-
producing teratomas,39 we are not aware of an association
between CAH and teratoma. This patient was also diag-
nosed with a TOA 2.5 years after her cyst surgery. She was
not sexually active, and no possible source of infection was
identified, but she also had a history of lower genital tract
surgery in infancy. TOA is a very rare finding in virginal girls
and there are only a few case reports; suggested
mechanisms were previous abdominal or genital surgery,
genitourinary abnormalities, genitourinary or gastrointes-
tinal spread, and bacteremia.40
Our retrospective study has considerable missing data,
and the quality of information recorded varied. Some
findings were not verified, and different laboratories used
different hormone assays. Moreover, this study was
conducted in a selected population of girls who were
referred to a pediatric endocrinologist, which might also
introduce a bias.
In conclusion, it is helpful to stratify girls with ovarian
cysts according to age, because etiology and clinical findings
might differ and smaller cysts might be clinically important
in prepubertal children. Most of our patients with ovarian
cysts had a favorable prognosis without any intervention,
but some had important coexisting problems or
complications such as tumors, torsion, CPP, and MAS.
Hence, these patients should be evaluated thoroughly and
treated by a multidisciplinary team.
Acknowledgments
We are immensely grateful to Stephen J. Winters, MD,
Professor of Medicine, and Ayca Erkin Cakmak, MD, MPH,
for their valuable comments on earlier versions of this
report.
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