Case Presentation
A 19-year-old woman presented with a onemonth
history of abdominal swelling and pain.
She was gravida 1, parity 1 with a 1 year-old child.
She delivered by cesarean section at 38th weeks
of gestation. During her antenatal period, we did
not observe any ovarian mass on ultrasonographic
examinations. Upon admission to the emergency
unit, she was referred to the radiology for an abdominal
ultrasound examination which revealed
73x60 mm in diameter, heterogeneous, ill-defined
bordered mass with solid and cystic components
located in the left ovary (Figure 1, 2). Also massive
intraabdominal ascite and heterojenity on major
omentum were found during abdominal tomography
(Figure 3). CA-125 was slightly elevated to
39.9 U/mL (normal 35 U/mL). While inhibin was
not ordered in pre-operative period, other tumor
markers (CA19-9, CA15-3, AFP, CEA) were in
normal limits. The patient underwent an exploratory
laparotomy. At the surgical staging, eight liters
of ascites was aspirated and a 10x9x9 cm in diameter,
lobular, with papillary projections on surface
and white-qray in color, heterogenous mass with
solid and cystic components in the left ovary was
found. Left salpingooophorectomy, partial omentectomy,
removal of implants on peritoneal surfaces
and peritoneal cytology were performed. Also
during exploration, multicystic and firm nature of
the right ovary was detected and wedge resection
was performed. The rest of the abdomen, including
all peritoneum was explored. Multiple intraabdominal
metastases with <2 cm in diameter, on the
peritoneal surfaces of bladder and douglas were
excised. Partial omentectomy was also performed
due to suspicious omental metastatic implants. The
uterus and bilateral tubes were normal. The cell
block on the ascitic fluid was positive for atypical
cells. Pathological report confirmed the diagnosis
of JGCT with all excised peritoneal materials were
invaded by the tumor in addition to the mature adipose
tissue observed on omentum. On microscopic
examination, the neoplastic granulosa cells were
lining cystic follicles and on immunohistochemical
staining, inhibin activity was found to be positive.
She was placed in FIGO stage IIIB. Six cycles of chemotherapy was planned as adjuvant theraphy
and she is still under regular follow-up.
Fig 1: A transvaginal ultrasonogram demonstrating a multilocular
tumor, measuring 7x6 cm in diameter, with
dominant solid components and irregular margins.
Fig 2: Tumoral mass exhibiting cyctic features.
Fig 3: Axial contrast-enhanced CT image of the lower abdomen
and pelvis shows a mass with solid and cystic
components in the left ovary. Note also intraabdominal
massive ascite.
Discussion
Juvenile granulosa cell tumors (JGCTs), found
in only 5% of all granulosa cell neoplasms, are rare
ovarian tumors and it is important that all gynecologic
oncologists should be aware of this rare
tumor, its clinical presentation, and appropriate
surgery.
Adnexal masses during pregnancy are relatively
rare, with a reported incidence of 1/81 to 1/8,000
pregnancies.[] Most of these adnexal masses disappear
as the pregnancy progresses. Ultrasonography
is often useful in detecting pelvic masses and distinguishing
cystic and solid features. The ultrasonographic
detection rate for adnexal masses during
pregnancy is approximately 1%.[] However, some
adnexal masses are relatively difficult to diagnosed
due to the mass itself, the imaging quality, or the
experience of the sonographer.
Generally GCTs are characterized by a low malignant
potential, local spread, late recurrences and
a high survival rate. About 80% JGCTs occurring
in children result in isosexual precocity. After puberty,
the JGCTs usually present with abdominal
pain or swelling. Likewise abdominal distension,
as in our patient, due to the tumoral mass and ascite
was the presenting symptom without any endocrinological
abnormality.
The majority of JGCTs are unilateral and early
stage tumors, whereas advanced stage JGCTs are
not commonly encountered. Our patient was diagnosed
in stage IIIB and the disease was progressed
or occured during the last one year of period. Since
we performed routine ultrasonographic evaluations
several times in antenatal period, we know
that our case did not have any adnexial mass during
her pregnancy. Advanced stage JGCTs reported
in the literature were diagnosed after the beginning
of symptoms so in these cases we do not have any
knowledge regarding how long these tumors had
been present. However we can consider that, in our
patient the tumoral mass has been present or progressed
or occured for last one year of period, since
it is now one year that the woman has delivered.
The primary management of JGCTs is surgical[]
and in young girls with stage IA disease, a unilateral
salpingooophorectomy is performed, as the majority
of the JGCTs are unilateral. At laparotomy, a
careful inspection of the contralateral tube, intraabdominal
organs, and peritoneal surfaces, along
with the sampling of pelvic plus paraaortic lymph
nodes is recommended.[] Since contralateral ovarian
involvement is uncommon, wedge biopsy is
not necessary if the ovary appears grossly normal.
Complete primary surgical staging included at
least a unilateral salpingooophorectomy with pelvic
washings, peritoneal assessment, partial omentectomy,
and pelvic and paraaortic lymph node
sampling performed at initial surgery or within 3
months from the initial surgery were also recommended.[] In the present patient, left salpingooophorectomy,
partial omentectomy, wedge resection
of right ovary, removal of implants on peritoneal
surfaces and peritoneal cytology were performed
and retroperitoneal lymph node sampling, though
not performed, would have been appropriate.
Chemotherapy should be initiated promptly
for women with stage IC to IV JGCTs after surgery.
And the most commonly used regimen is a
combination of bleomycin, etoposide, and cisplatin
(BEP). Etoposide and cisplatin (EP); cyclophosphamide,
doxorubicin, and cisplatin (CAP);
platinum agent alone or taxanes also seem to be
effective in sex cord stromal tumors of the ovary.
[] Radiotherapy, though not very effective, may
be used for patients with advanced or recurrent
JGCTs.[] In the present case, she underwent BEP
chemotherapy in our oncology department and she
did not complete her planned chemotheraphy, yet.
Although not reported in JGCTs, a limited number
of recent studies have demonstrated a response
to hormonal treatment in adult GCTs. For example,
Freeman and Modesitt[] reported two patients with
recurrent adult GCTs responding to the aromatase
inhibitor, anastrozole. Hardy et al.[] also reported
a patient with estrogen receptor-negative and progesterone
receptor-positive GCT responding to
megestrol and tamoxifen. Although these results
are encouraging, all are limited number of studies
in adult GCTs and we can not consider these reported
treated cases as routine regimens.
GCTs are considered to be of low malignant potential
and are characterized by their slow growth
and late recurrence. Stage is clearly the most important
prognostic factor. The reported 5-year survival
rate for patients with stage I disease ranges from
75% to 90%. However advanced FIGO stages are
associated with early relapses and poor outcome.[]
A number of recent studies have evaluated the
significancy of prognostic factors in GCTs. In this
regard, gsp oncogene (derived from Gs protein)
and its products, activating the cAMP-dependent
signalling and leading to abnormal cell proliferation,
were demonstrated in 30% juvenile GCT cases.[] In these gsp-positive patients, a more aggressive
pattern were observed. Additionally, another
predictor factor for JGCT survival was considered
as Forkhead box L2 (FOXL2) protein.[] In agressive
JGCTs, FOXL2 expression was found to be
absent or decreased.[] Unfortunately, we did not
have any opportunity in our patient for evaluating
the presence of these gene products and by this
way for yielding the very agressive and rapid progression
of the mentioned tumor.
As a result, we can conclude that; although
these tumors are seen in early stages and agressive
pattern is generally not expected, our patient
was diagnosed at advanced stage and the disease
can be accepted as occured or progressed in only
last one year. Due to this feature, as long as our
knowledge, it was the first reported case regarding
the occurence history of the juvenile granulosa cell
tumor in adult.
