Journal of Cancer Therapy, 2013, 4, 1391-1394 Published Online October 2013 (
Investigation of the Cause of Precocious Puberty in an
8-Year-Old Girl Ended up in Juvenile Granulosa and
Theca Cell Tumor of the Ovary
Mahtab Ordooei1, Mojgan Karimi-Zarchi2*, Golnaz Malekzadeh3, Mansour Moghimi4
1Department of Pediatrics, Pediatric Endocrinologist, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2Gynecology
Oncology Department, Shahid Sadoughi Hospital, Yazd, Iran; 3Shahid Sadoughi University of Medical Sciences, Yazd, Iran;
4Department of Pathology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Email: *
Received March 6th, 2013; revised April 5th, 2013; accepted April 14th, 2013
Copyright © 2013 Mahtab Ordooei et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Isosexual precocious puberty in girls has several etiologies. Juvenile granulose cell tumor is one of the rarest causes that
only stands for 1.5% of ovarian cancers. This tumor mostly encounters in first 2 decades of life. This paper is a report of
an 8-year-old girl with precocious puberty that within five months developed breast enlargement followed by menarche.
Works which are done to find the underlying cause of precocious puberty revealed juvenile granulosa cell tumor in her
left ovary. She then under went laparoscopic surgery and 3 courses of chemotherapy. She did not experience any vagi-
nal bleeding after that and the serum level of estradiol lay among its normal ranges, but after that the tumor relapsed and
presented as abdominal pain and a huge mass which under went resection of all afflicted tissues. After 2 courses of che-
motherapy, her status deteriorated and unfortunately she died after 6 months from the time of diagnosis. Treatment for
this disease is consists of resection surgery and chemotherapy. If this tumor is diagnosed in its early stages, it will be
curable, but in its advanced stages, up to 80% of patients die from recurrent tumors. The reported patient was diagnosed
at stage IIIC that had poor prognosis.
Keywords: Precocious Puberty; Juvenile Granulosa Cell Tumor; Ovary
1. Introduction
Juvenile granulosa cell tumor of the ovary (JGCT) is a
subset of ovarian cancers and stands for almost 5% of all
ovarian malignancies [1]. It can be distinct from its adult
type that mostly occurs in post menopausal women due
to different clinical and pathological features such as
hirsutism, abdominal discomfort and abnormal vaginal
bleeding. Juvenile type has higher mitotic activity and
nuclear atypicality as well as the expression of PCNA
and p53, but has poor prognosis in comparison to adult
type [2]. This tumor has the potential to produce hor-
mones that lead to early presentation and diagnosis [3].
The complaint that is common among these patients is a
palpable mass in lower abdomen. Ascites in 10% of them
is reported [4]. This tumor can present in divers ages
from infancy to teenage but it mostly presents in the age
of 8 or 9 years old [5].
This tumor is rarely reported before [6-15], this paper
is a report of an 8-year-old girl who presented iso sexual
precocious puberty and works which are done to find the
underlying cause ended up in Juvenile granulosa and
theca cell tumor of the ovary.
2. Case Presentation
The patient was an 8 year old girl from Yazd in an only
child family from high socioeconomic level with the
height of 142 cm and weight of 34 kg, who presented
breast enlargement compatible with Tanner III. About
five months from first bud of breasts, she started vaginal
bleeding but no presentation of pubic or auxiliary hair.
She was referred to pediatric endocrinologist to investi-
gate the cause of precocious puberty. In physical exam
the vital sign was stable everything was normal but a
large mass in left side of abdomino pelvic cavity was
palpated. No peripheral lymphadenopathy or organo-
megaly was detected. She had no complaint of pain or
nausea, vomiting or other complaint of any kind. The lab
*Corresponding author.
Copyright © 2013 SciRes. JCT
Investigation of the Cause of Precocious Puberty in an 8-Year-Old Girl Ended up in Juvenile Granulosa
and Theca Cell Tumor of the Ovary
results indicated normal thyroid function and Cell Blood
Count (CBC) but impaired serum level of gonadal hor-
mones. Folicle stimulating hormone (FSH) was 0.2 (0.1 -
4.3 IU/lit), luteinizing hormone was 1.9 (0.1 - 5 IU/lit),
stradiol was 120.9 (6 - 27 pg/ml), serum cortisol of 8 AM
was 15 μg/dl (5 - 23 μg/dl). Advanced bone age was also
detected that was around 12 years old. Other lab tests
consist of liver function test was normal but a high Lac-
tate dehyrogenase was reported which was 1040 U/l (up
to 580 U/l). Alkaline phosphatase was 664 U/l (180 -
1200) and urine analysis showed moderate amorph urate
crystal. Electrolytes consist of Na, K, Ca, P were all in
their normal ranges. In the sequence order abdominopel-
vic sonography was done. It showed a lobulated echo-
genic solid mass in left part of abdomen with the diame-
ter of 4 cm and free fluid in abdomen especially in pelvis
and under the liver. For further assessment CT scan with
intravenous contrast was done. The result showed a large
20 * 11 cm multiloculated cystic mass with marked sep-
tation and loculation in left side of abdomino pelvic cav-
ity that has the pressure effect on the pelvic and abdomi-
nal content. Ovarian cystadenoma, mucinous cystade-
noma or other pelvic masses were suggested. Some of
tumor markers also were elevated. Carbohydrate antigen
19-9 was 6.2 U/ml (up to 39), carbohydrate antigen 125
was 469 U/ml (up to 35), carcinoembryonic antigen
(CEA) was 0.44 ng/ml (0.0 - 5), beta HCG (beta Human
Chorionic Gonadotropin) was 0.1 mIU/ml (up to 5.3),
alpha feoto protein was 1.2 IU/ml (0.0 - 5.8) and inhibin
A was 320 pg/ml (<2.2 pg/ml). Patient was referred to
gynecologist and the tumor was resected by Laparo-
scopic surgery. Histopathology and ascites fluid cytology
confirmed the rare ovarian tumor of Juvenile granulosa
and theca cell. High mitotic activity with wide necrotic
parts and calcified and bizarre nuclei was seen (Figures
1 and 2). In immunohisto chemistry CD99 (Cluster of
Differentiation 99), BCL2 (B-cell lymphoma 2), PR
(progesterone receptor), CKAE1/AE3 (Cytokeratin AE1/
AE3) was reported positive which is compatible with
juvenile granulose cell tumor (Figures 3 and 4). Then
Figure 1. JGCT with high mitotic rate and moderate to
abundant eosinophilic to vacuolated cytoplasm and round,
hyperchromatic nuclei lacking grooves (H & E 40X).
Figure 2. JGCT with pseudopapillary architecture (H & E
Figure 3. JGCT, Diffuse membranous CD99 positivity is
characteristic (IHC 40X).
Figure 4. JGCT, patchy weak cytoplasmic staining for
CKAE1/AE3 (IHC 40X).
chemotherapy of BEP consists of Bleomycin, Etoposide
and Cisplatin started for her. After the third course of
chemotherapy the tumor relapsed with the presentation of
abdominal pain and huge mass. Because of the relapse of
tumor patient went under complete resection of tumor,
left oophorectomy, appendectomy and resection of intes-
tine and peritonea which the tumor adhered to them.
Only uterine, right ovary and fallopian tube were pre-
served. The stage of the tumor was equivalent to III C.
Chemotherapy of BEP continued for her but after the
second course, her status deteriorated. She had dyspnea
which then hospitalized and metastasis to lungs was de-
tected. Despite all procedures done on her unfortunately
she died after 6 months passed from diagnosis.
3. Discussion
Ovarian juvenile granulosa cell tumors are rare malignant
Copyright © 2013 SciRes. JCT
Investigation of the Cause of Precocious Puberty in an 8-Year-Old Girl Ended up in Juvenile Granulosa
and Theca Cell Tumor of the Ovary
tumors afflict young girls. As this tumor mostly secreted
hormones, the most common presentation is precocious
puberty, premature thelarche and vaginal bleeding [16]
that all goes along with this reported patient’s presenta-
tion. Due to tumor derived estradiol, she had advanced
bone age compatible with the age of 12 years old.
On CT scan and sonography, JGCT most typically
appears as large, multilocular mass [17]. In this case, also
a large multi loculated cystic mass with marked septation
and loculation in left side of abdomino pelvic cavity was
Diagnosis of JGCT in pathology may be confused with
other ovarian tumors with pseudopapillary pattern; im-
munohistochemistry can be used in more problematic
cases [18]. These tumors are characteristically positive
for inhibin, calretinin, Vimentin and keratin [19]. In this
patient, CD99 and Cytokeratin AE1/AE3 were reported
positive. In 6 cases reviewed by Kavuri et al, diffuse
positivity for vimentin in all of them was reported but the
staining for cytokeratin (AE1/AE3) and calretinin was
negative. Four cases expressed CD99 and 1 case was
positive for inhibin [20].
The most important prognostic factor is tumor stage.
The tumors with the size of more than 5 cm, mitotic fig-
ures more than 10 in hpf and The more degree of nuclear
atypia have poor prognosis [21,22]. The treatment is also
related to the stage of the tumor, but selective treatment
in early stages is unilateral salpingo oophorectomy and
then starting the chemotherapy [23]. Cisplatin had shown
good results in treatment of these patients [24]. BEP
(Bleomycin, Etoposide and Cisplatin) is also recom-
mended for chemotherapy [24] but if the tumor excised
completely in early stages, adjuvant therapy may not be
necessary [25].
Inhibin is dimeric glycoprotein secreted from ovarian
granulose cells. It is a good marker to follow up patients
and diagnose any recurrence [26-28]. In previous studies,
Activin B was also reported as a good marker to monitor
the patients [29].
As this tumor mostly presented in juveniles, preserva-
tion of fertility in patients is an important issue which
can be reached by early diagnosis, tumor resection, che-
motherapy and strict follow up. The patient’s disease was
diagnosed less than 5 months and went under surgery
twice and 5 courses of BEP chemotherapy which lead to
regression in breast size and decrease in the serum estra-
diol level but unfortunately the tumor outnumbered all
treatments and she expired after 6 months.
4. Conclusion
According to the high prevalence of functional cysts in
comparison to neoplastic masses in childhood, malign-
nancies may be underdiagnosed and mismanaged. So
consideration of the clinical features along with preclini-
cal investigations can result in earlier diagnosis and a
better prognosis.
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and Theca Cell Tumor of the Ovary
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