Pediatr Blood Cancer 2005;44:167–173
Pediatric Ovarian Tumors: A Review of 67 Cases
Kris Ann P. Schultz, MD,1Susan F. Sencer, MD,2Yoav Messinger, MD,3
Joseph P. Neglia, MD, MPH,1and Marie E. Steiner, MD1*
Pediatric ovarian tumors are an uncommon but impor-
tant form of childhood cancer. Ovarian tumors are the
most frequent neoplasms of the female genital tract in
childhood  and are generally considered to account
for approximately 1% of all malignancies in patients ages
0–17 years . Ovarian masses include neoplastic and
non-neoplastic processes. Non-neoplastic conditions in-
clude follicular cysts, corpus luteal cysts, and endome-
triomas. Neoplastic processes include both benign tumors
such as mature cystic teratomas as well as highly malig-
potential that frequently follow a benign clinical course.
Various classification and nomenclature systems have
been developed to describe the spectrum of ovarian
tumors. Generally these tumors are classified into three
main categories including epithelial, stromal, and germ
have noted a predominance of germcell tumors. Thisis in
contrast to the adult literature, which notes the predomi-
nance of tumors of epithelial cell origin . This dif-
ference highlights the importance of considering patient
age when evaluating ovarian pathology.
Germ cell tumors include teratomas and gonadoblas-
tomas as well as endodermal sinus tumors, also called
and choriocarcinomas. Teratomas include both immature
(malignant) and mature (benign) forms. Immature tera-
tomas are classified according to their level of differentia-
tion . Histologic level of differentiation determines the
level of malignancy. Gonadoblastomas occur exclusively
in patients with dysgenetic gonads and are classified as
benign tumors, however, malignant dysgerminomas are
frequently found within these tumors.
Children may also present with non-germ cell tumors
including sex cord-stromal tumors and epithelial tumors.
Sex cord stromal tumors include thecoma–fibroma,
Sertoli–Leydig cell tumors and granulosa cell tumors.
Juvenile granulosa cell tumors follow a very different
clinical course than granulosa cell tumors in adult women
and although they have malignant potential, they com-
monly follow a benign clinical course.
Epithelial tumors, including cystadenoma in benign,
borderline, and malignant forms, are common in adult
women, though much less frequent in children. Small cell
Background. Ovarian tumors are uncommon
but important childhood neoplasms. Procedure.
We reviewed records of 67 pediatric patients
presenting to three pediatric referral centers
from 1980 to 2003. Results. Thirty patients had
benign tumors. Thirty-seven patients had malig-
nant tumors: 11 immature teratomas, seven
malignant mixed germ cell tumors, seven juve-
nile granulosa cell tumors, five dysgerminomas,
two endodermal sinus tumors, two serous
papillary cystadenocarcinomas, one small cell
carcinoma, one anaplastic sex-cord tumor, and
one undifferentiated sarcoma. More than half
presented with abdominal pain. Forty-six per-
cent had an abdominal mass at the time of
presentation. Other signs and symptoms in-
cluded poor appetite (15%), urinary symptoms/
urinary infection (9%), menstrual changes (9%),
and weight loss (6%). Precocious puberty was
noted in seven patients. Torsion was seen more
often in patients with benign tumors (23 vs. 8%);
two patients had both torsion and acute
appendicitis. The neoplasm was an incidental
finding in 12 patients. Conclusions. Fifty-five
percent of the 67 ovarian tumors presenting to
our centers were malignant. Pain was the most
common symptom, although presence of an
abdominal mass was frequent, and other symp-
toms non-specific. Almost all neoplasms pre-
sented as unilateral masses and rarely were
metastatic at diagnosis. Ovarian tumors must be
considered in the differential diagnosis of young
girls with abdominal pain, mass, or other non-
specific symptoms. Pediatr Blood Cancer 2005;
? 2004 Wiley-Liss, Inc.
dysgerminomas; epithelial tumors; germ cell tumors; granulosa cell tumors;
ovarian neoplasms; precocious puberty
1Department of Pediatrics, University of Minnesota, Minneapolis,
2Children’s Hospital of Minneapolis, Minnesota
3Children’s Hospital of Saint Paul, Minnesota
Grant sponsor: Children’s Cancer Research Fund.
*Correspondence to: Dr. Marie E. Steiner, Department of Pediatrics,
Mayo Mail Code 484, 420 Delaware Street SE, Minneapolis, MN
55455. E-mail: email@example.com
Received 18 March 2004; Accepted 25 August 2004
? 2004 Wiley-Liss, Inc.
carcinomas of the ovary occur very rarely, though this
. These tumors usually are found at an advanced stage
and are generally considered to have a poor prognosis.
This study summarizes all ovarian tumors diagnosed at
three pediatric referral centers in recent years.
MATERIALS AND METHODS
We identified 67 patients ages newborn to 18 years
presenting to the University of Minnesota and Children’s
Hospitals of Minneapolis and Saint Paul from 1980 to
pediatric oncology care.
Case records were obtained by searching tumor regis-
tries at the participating hospitals as well as by search-
ing medical records information via ICD-9 codes. All
available medical records were reviewed. Only those
patients with primary ovarian tumors were considered.
Patients with metastasis to the ovary were excluded. Non-
neoplastic processes such as simple cysts were also
excluded from this review. This review follows the WHO
pathohistological classification of ovarian tumors (WHO,
1973) and International Federation of Gynecology and
Obstetrics (FIGO) staging criteria.
children less than 6 years of age, malignant tumors were
more common than benign tumors. Nearly half of all
malignant tumors were in children ages 7–12 years.
Mature teratomas were more common in adolescence.
Constitutional chromosomal analysis revealed: del
(10q23) in a patient with grade IV stage IV mixed germ
cell tumor; trisomy (XXX) in a patient with mixed germ
cell tumor; 46,XYin a phenotypic female with dysgermi-
noma; 46,XYin a hermaphroditewith stage IA dysgermi-
noma; 45,XO/46X psu dic Y in a patient with Turner
syndrome and bilateral gonadoblastoma with unilateral
Signs and Symptoms at Presentation
More than half of our patients presented with abdo-
minal pain as the primary symptom (Fig. 3). Forty-six
percent presented with abdominal mass. Torsion was fre-
teratomas, had both pathologically confirmed torsion and
acute appendicitis at the time of surgery. Twelve patients
neoplasm was found either during a routine health care
visit or during radiographicscreening for another medical
children with benign versus malignant tumors. However,
patients with benign masses, particularly mature cystic
teratoma, were more likely to present with torsion (23 vs.
8%). Precocity was most common in children with
juvenile granulosa cell tumor (five of seven patients).
Overall, 93% (n¼62) of tumors were unilateral; 58%
were right-sided. Bilateral tumors included bilateral
gonadoblastoma with unilateral dysgerminoma, bilateral
papillary serous adenocarcinoma, bilateral mucinous cys-
tadenoma, and bilateral mature teratomas. Contralateral
ovarian findings included mature cystic teratoma, lym-
phangioma, and simple cysts.
Abdominal radiograph, abdominal ultrasound and
computed tomography were frequently performed (see
TableI).Three patientsunderwent exploratorylaparotomy
prior to anyimaging study due to a presumed diagnosis of
Age at diagnosis of benign tumors.
granulosa cell tumors.
Age at diagnosis of malignant tumors including juvenile
168Schultz et al.
The most common benign tumors were cystic terato-
mas. Cystadenomas were also noted, one with borderline
features (see Tables II and III).
Of the malignant tumors, immature teratomas were the
most common. Seven patients had juvenile granulosa cell
tumors; these were often associated with precocious
nant germ cell tumors. Five patients had dysgerminomas;
two of these were otherwise healthy and had normal
each with a palpable pelvic mass at the time of presen-
tation. One patient had unilateral endodermal sinus tumor
with a contralateral mature cystic teratoma. Other malig-
nancies observed included small cell carcinoma, cystade-
nocarcinoma, papillary adenocarcinoma, undifferentiated
sarcoma, and anaplastic sex cord tumor with Sertoli–
Leydig and granulosa-theca cell forms.
Patients with benign cystic teratomas had AFP, CEA
and b-hcg in the normal range, however, LDH and ESR
were often elevated. Patients with juvenile granulosa cell
tumors and precocious puberty often had normal AFP, b-
hcg and CEA, however, estradiol, and testosterone were
frequently elevated. One patient with a juvenilegranulosa
cell tumor had increased AFP and inhibin with a normal
b-hcg and CEA.
Elevated tumor markers seen in immature teratomas
included increased AFP, LDH, and CA-125. AFP was
elevated in 10 of our 11 cases. CA-125 was measured
in only two cases of immature teratoma and was found
to be elevated in both. b-hcg was normal in all but one
case where it was found to be minimally elevated and
resolved following treatment. Both patients with endo-
elevated CA-125 and LDH. b-hcg was normal in each
All tumor markers were negative in patients with
sarcoma. A patient with small cell carcinoma presented
study to have hypercalcemia at the time of presentation.
One patient diagnosed with an anaplastic sex cord tumor
was found to have an elevated CA-125.
Tumor marker elevation in mixed malignant germ
cell tumors depended heavily on the tissue components
present. One patient with precocious puberty was found
to have a mixed germ cell tumor with marked eleva-
tion of AFP, b-hcg, DHEAS, and testosterone. Mixed
Signs and symptoms at presentation.
TABLE I. Studies Performed to Establish Diagnosis
Initial diagnostic studies%
Abdominal ultrasound, no CT
Abdominal CT, no ultrasound
Both CT and ultrasound
Magnetic resonance imaging
Exploratory lap prior to imaging
CT, computed tomography; lap, laparotomy.
Abdominal radiographs were frequently performed in addition to other
Pediatric Ovarian Tumors 169
TABLE II. Characteristics of Patients With Benign Tumors
Diagnosis%NAge range (y)Mean age (y)Associated medical conditions
Cystic teratoma35.8 244–1711.5 Tuberous sclerosis
Gastroschisis with short bowel syndrome
Congenital lumbosacral myelomeningocele
TABLE III. Characteristics of Patients With Malignancies
Diagnosis%N Stage/gradeTreatment/outcomeAge at dx
Stage IA, grade I
Stage IA, grade II
Stage IA, grade II–III Two resection, one resection and
Stage IC, grade IIResection, chemo, NED at 4 y F/U
Stage IV, grade IIIResection, chemo, NED at 12 y F/U
1Stage IA Bilateral oophorectomy, NED at
4 y F/U
Resection, recurrence at 2 y, curr
Resection, chemo, NED at 9 y F/U
Bilateral oophorectomy, recurr,
XO with XY mosaicism
Endodemal sinus tumor3.0
Resection, chemo, NED at 5 y F/U
Resection, chemo, NED at 1 y F/U
Juvenile granulosa cell
Resection, NED at 1–4 y F/U
Resection, NED at 1 y F/U
Resection, NED at 1 y
Precocious puberty at dx
Estrogen hepatopathy at dx
Ascites, respiratory distress
Mixed germ cell tumor 10.5
1Stage I Resection, chemo, recurrence,*7 y AVM, deafness, precocious
1Stage IResection, recurr, resection, chemo,
Resection, chemo NED at 11 y F/U
Resection, chemo, NED at last F/U
Resection, chemo, NED at 6 y F/U
Family history of ovarian
Factor V Leiden heterozygote
Resection, chemo, NED at 2 y F/U
Resection, chemo, resection, chemo,
NED at 2 y F/U
Resection, chemo/XRT, autoBMT,
NED at 5 y F/U
Resection, chemo, persistent
disease, chemo, died
Resection, chemo, remission, second
tumor (see text)
Resection, chemo, recurrence,
Small cell carcinoma 1.51Stage III12 y Hypercalcemia at diagnosis
Stage IIc, grade I
Undifferentiated sarcoma 1.51 Stage I10 y Duplicated renal collecting
Family history of ovarian
Anaplastic sexcord tumorþ
1.51 Unstageable14 y
y, year(s); NED, no evidence of disease; *, outcome unknown; F/U, follow-up; dx, diagnosis; chemo, chemotherapy; AVM, arteriovenous
malformation; autoBMT, autologous bone marrow transplant; þ, Sertoli–Leydig and granulosa-theca cell forms.
170Schultz et al.
germ cell tumors including endodermal sinus tumor
components were associated with elevated AFP. For all
tumors, abnormal lab values normalized following treat-
ment and in two cases tumor marker elevation helped to
Treatment of benign tumors was largely surgical. Five
patients were treated with cystectomy alone. Twenty-two
patients underwent unilateral salpingo-oophorectomy.
Three patients underwent unilateral salpingo-oophorect-
omy with biopsy or cystectomy of the contralateral ovary.
Eight patients also underwent appendectomy; two of
these patients had histological findings consistent with
Even with malignant tumors, conservative therapy was
and diagnosesof thepatients studied.Unilateral salpingo-
salpingo-oophorectomy was performed in one patient
with stage IIIC papillary serous adenocarcinoma and in
patients with dysgerminoma in the setting of chromo-
somal abnormalities predisposing to malignancy. One
patient with stage IV mixed germ cell tumor underwent
radical resection following initial chemotherapy. Perito-
neal fluid sampling, lymph node dissection, and partial
omentectomy were frequently performed. Small bowel
resection was required in one case.
Metastasis was rarely noted at the time of diagnosis
(Table IV). Peritoneal gliomatosis was seen in two
patients, both with immature teratomas. Three patients
eventually relapsed despite having no initial evidence of
Post-operative vaginal bleeding was observed in one
patient following resection of her juvenile granulosa cell
including neutropenic fever and infection as well as drug-
specific complications, occurred. Little information on
eventual fertility is available for the patients in our study
noted to have premature ovarian failure by chart records,
although the eventual rate of ovarian failure will likely be
One patient treated with surgical resection and chemo-
therapy for an undifferentiated sarcoma of one ovary was
later found to have virilization and a Sertoli–Leydig cell
tumor of the contralateral ovary. This patient has normal
chromosomes and was the only patient in our study to
develop a second ovarian malignancy.
children and adolescents and found a malignancy rate of
55%, slightly higher than previously observed. Reported
rates of malignancy vary by study. Some studies have
included simple cysts and torsional cysts as part of anal-
yses of ovarian masses [6–9] while some have includ-
ed only neoplastic conditions [10–12]. Classification of
borderline or premalignant tumors varies between studies
as well. Some studies have included juvenile granulosa
cell tumors in the malignant category [7,8,10–12] while
others have classified them as benign .
rates of malignancy: first, all three hospitals analyzed in
this study are referral centers. Each facility has several
pediatric oncologists on staff. Also, our search methods
(OncoLog and Cancer Data Services) may tend to include
TABLE IV. Frequency and Timing of Metastasis to Various Sites
Timing of metastasisNLocation
At time of diagnosis6
Liver and omentum
After initial therapy
Although only six patients were noted to have metastases at the time of
diagnosis, some patients had metastases to more than one site.
TABLE V. Complications Seen Following Therapy
Decreased pulmonary function
Sensorineural hearing loss
Persistent abdominal pain
Post-operative vaginal bleeding
Premature ovarian failure
ARDS, acute respiratory distress syndrome.
Pediatric Ovarian Tumors 171
disease were identified using ICD-9 codes, which may
have missed some cases.
neoplasms of 41.4%. This study was a retrospective
polis. This study found 12 benign teratomas, three
malignant germ cell tumors, two immature teratomas,
three granulosa-theca tumors, two Sertoli–Leydig cell
tumors, two lymphomas, and one each of mucinous
cystadenoma, cystadenocarcinoma, small cell carcinoma,
fibroma and hemangioma. Hassan et al.  in Athens
In this review, 77.2% of cases were benign. Malignancies
constituted nearly 16% and the remainder were border-
line. In their study, mature cystic teratoma was the most
of all malignant tumors. Freud et al.  reviewed 34
ovarian masses in Tel Aviv in girls from birth to 17 years.
Their review found 18 non-neoplastic processes and 16
neoplasms of which 50% were malignant.
of age who were diagnosed with ovarian tumors. In their
review, 75% were benign, 20% malignant, and 5% poten-
and 33 of epithelial origin. Eighteen tumors were of
reviewed; this included simple cysts and torsion-related
cysts, which may account for the low rate of malignancy
(18/91). In their study, ultrasound was 100% accurate in
diagnosing the process as occurring in the ovaries, how-
ever, ultrasound was not able to distinguish benign from
malignant neoplasms. Among neoplastic masses in their
study, the risk of malignancy for patients less than 8 years
was only 3% though this risk increased to 33% in patients
9 years and older .
In our study, juvenile granulosa cell tumors were
classified as malignant due to their malignant potential,
thoughall ofthe cases inour series behaved ina clinically
benign fashion. Each of the seven patients with juvenile
granulosa cell tumors in our study was treated with either
unilateral oophorectomy or unilateral salpingo-oophor-
ectomy. None had chemotherapy. None have evidence
of recurrence at this time. Although our patients did not
develop metastasis or recurrence, Calaminus et al. 
noted eight children with stage IC juvenile granulosa cell
tumors, four patients with stage IIC, and one patient with
stage IIIC disease. Adjuvant chemotherapy was used for
eight of these patients and additionally for one patient
in stage IA whose pathologic diagnosis included a high
mitotic index. During a follow-up period of 168 months,
they noted an event-free survival of 0.75?0.07. They
concluded that multi-drug therapy could be useful in
augmenting survival in juvenile granulosa cell tumors,
especially those of advanced stage. Thus, while all of the
patients in our study had juvenile granulosa cell tumors
that have seemed to behave in a clinically benign fashion,
this is not the universal experience.
Despite somewhat different findings between studies,
all studies found a significant number of ovarian masses
were malignant. Fortunately, ovarian malignancies in
children are frequently found at an early stage and most
 reported survival in all patients with benign tumors
and seven of ten patients with malignant lesions. Brown
et al.  noted two deaths in patients in their study that
included 18 malignancies. Both were in patients with
endodermal sinus tumors. Despite epithelial cancers of
advanced stage (two patients of stage III, both with posi-
tive second-look procedures), no patients with epithelial
A review by Imai et al.  included 23 patients with
malignancies, only three of whom died within 4 years of
As features and outcomes of pediatric ovarian tumors
are more thoroughly studied, efforts are expanding to
of ovarian function and fertility.
Though uncommon in children, the clinical spectrum
of ovarian tumors ranges from largely benign mature
teratomas to life-threatening, widely metastatic cancers.
Using modern radiographic, surgical, and pathologic
techniques available at pediatric referral centers, we
found approximately half of ovarian tumors occurring in
other symptoms non-specific. Precocious puberty and/or
increasing abdominal girth may be concurrent findings.
Torsion was occasionally found at the time of diagnosis,
more frequently with mature cystic teratomas than with
malignant tumors. Almost all neoplasms presented as
unilateral masses and rarely were metastatic at diagnosis.
Almost half the patients presented at 7–12 years of age.
The option of conservative surgical therapy depends on
the stage of disease at the time of diagnosis. Most patients
with malignancies clinically do well with few recurrent
tumors. It is critical to consider the diagnosis of ovarian
in the differential diagnosis of even very young girls with
abdominal and endocrine symptoms.
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Pediatric Ovarian Tumors 173