Malignant ovarian mixed germ cell tumour: a rare combination
MBBS, MRad, A Vijayananthan1,
MBBS, MRad, V Vadiveloo2, MBBS,
1 Department of Biomedical Imaging (Radiology), Faculty of
Medicine, University of Malaya, Kuala Lumpur, Malaysia
2 Department of Obstetrics and Gynaecology, Tengku Ampuan
Rahimah Hospital, Klang, Selangor, Malaysia
germ cell tumours are very rare and affect mainly young girls
and women. Due to this, the conservation of reproductive potential
is of great concern. One of the most remarkable advances in
oncology is in the treatment of malignant ovarian germ cell
tumours. Two histological groups are distinguished: dygerminomas,
equivalent to testicular seminomas, and non-dysgerminomatous
tumours. We report a case of a 30-year-old nulliparous woman
who presented with persistent per vaginal bleeding and was
found to have a malignant mixed germ cell tumour comprising
of both embryonal carcinoma and choriocarcinoma. © 2005
Biomedical Imaging and Intervention Journal. All rights reserved.
Keywords: Malignant mixed germ cell tumour, embryonal
Ovarian germ cell tumours comprise approximately 15% to 20%
of all ovarian neoplasms. They are rapidly growing neoplasms
that arise from primordial germ cells derived from the embryonal
gonad. Malignant germ cell tumours comprise less than 5% of
all ovarian neoplasms. The incidence of malignant ovarian
germ cell tumours range from 1 to 6 percent as reported in
the West and from 8 to 19 percent in Asia .
Two histological groups are distinguished: dygerminomas, equivalent
to testicular seminomas, and non-dysgerminomatous tumours.
The diagnosis suspected on physical examination, relies
on pelvic or transvaginal ultrasonography detection of a voluminous
ovarian mass responsible for abdominal discomfort and/or swelling.
However, this is only confirmed during the initial surgical
intervention. Tumour markers such as human chorionic gonadotropin
(HCG) and alpha-fetoprotein also contribute to the diagnosis,
the prognosis and follow-up of the disease.
We present a case of malignant mixed germ cell tumour comprising
of embryonal carcinoma and choriocarcinoma. The term “embryonal
carcinoma” was used in a study by Kurman et al., as
it is analogous to embryonal carcinoma of the adult testis
and can be distinguished from the endodermal sinus tumour
by its distinctive morphology, immunohistochemistry, and clinical
A 30-year-old nulliparous woman had significant persistent
per vaginal bleeding and was seen by a private obstetrician.
An ultrasound of the pelvis was done and it was said to be
normal at that time. She was treated with progestogens for
four cycles and her menstrual cycle resumed to being normal.
Six months later she presented again with per vaginal bleeding
and a repeat ultrasound revealed a pelvic mass. A diagnostic
laparoscopy was then done and deposits were found in both
adnexa but no biopsy was taken. She was once again treated
with progestogens for two cycles.
One month later she presented again with per vaginal spotting
for four weeks and was then referred to the gynaecology clinic
at University Malaya Medical Centre. She also complained of
lower abdominal pain but denied any other symptoms.
Physical examination revealed that she had slight pallor
and was afebrile. Vital signs were as follows: blood pressure
of 107/72 mmHg, pulse rate 114 bpm, respiration 18/min. She
had a distended abdomen with a firm, non-pulsatile, palpable
mass in the pelvis and extending up to just below the umbilicus.
There was mild periumbilical tenderness, but no guarding or
Rectal examination was negative for occult blood, and there
were no masses felt. There was no inguinal adenopathy. Past
history revealed that she had experienced menarche at age
12. Her menstrual periods were described as regular cycles
with normal flow. There was no family history of any gynaecological
[View this figure]
|Figure 1 Ultrasound examination
revealed a mass of mixed echogenicity in the right
adnexa (arrows). UB = urinary bladder
[View this figure]
|Figure 2 Computed tomography
scan of the pelvis revealed a highly vascular enhancing
mass (arrow) in the pelvis
Initial laboratory results revealed a normal complete blood
count, electrolytes, blood urea, creatinine and glucose, but
a low haemoglobin count of 91.6 g/L. Her urine pregnancy test
was positive. The patient underwent exploratory laparotomy
for suspected ectopic pregnancy, as ultrasound scan showed
an enlarged uterus with no gestational sac and a right heterogeneous
ovarian mass measuring 4 cm x 5cm x 2.5cm (Figure 1). A right
ovarian tumour with deposits on the uterus was found (Figure
2). Right cystectomy was then performed and a biopsy of the
uterine deposits was taken.
On gross pathologic examination, sections through the ovary
showed ‘a very haemorrhagic and necrotic tumour’.
Microscopic specimens determined the tumour to be a germ cell
tumour with embryonal carcinoma and choriocarcinoma elements
[View this figure]
|Figure 3 Photomicroscopy of mixed
germ cell tumour showing a combination of embryonal
carcinoma (arrowhead) and choriocarcinoma as evidenced
by the presence of a sheet of cytotrophoblasts surrounded
by syncytiotrophoblasts (arrow) elements
[View this figure]
|Figure 4 Intraoperative findings
showing deposits (arrow) on the uterine surface
A thoracic, abdominal and pelvic computed tomography (CT) scan
was then obtained to stage the tumour. CT scan showed a highly
vascular enhancing mass in the pelvis measuring 11.4cm x 11.3cm
x 11.0cm (Figure 4) with multiple hypodense lesions in the liver
and pancreas. There was no abdominal lymphadenopathy. Multiple
hyperdense nodules of various sizes were seen throughout both
lung fields and an enlarged pretracheal lymph node was also
evident. The tumour was classified as Stage IV.
Despite multiple chemotherapy regimes, serial ultrasound
five months later showed an enlarged uterus measuring 10.0cm
x 6.6cm x 9.0cm with two hypodense areas within it and a 2.8cm
x 4.7cm mass in the pouch of Douglas.
Six months later patient presented to the emergency department
with headache and unsteady gait for two days. Computed tomography
of the brain showed hemorrhagic cerebellar metastases. The
patients conditioned gradually deteriorated and she succumbed
to her illness two weeks later.
Ovarian germ cell neoplasms are thought to be derived from
primitive germ cells of the embryonic gonad. They constitute
the second largest group accounting for 15 to 20 percent of
all ovarian neoplasms. Malignant germ cell tumours comprise
less than 5 percent of all ovarian neoplasms .
In 1973, the World Health Organization classified germ cell
tumours as Dysgerminoma, Endodermal sinus tumour, Embryonal
carcinoma, Polyembryoma, Choriocarcinoma, Teratomas (Immature,
Mature, Monodermal), Mixed and Gonadoblastoma .
This initiative represented a major advance in terms of standardisation
of nomenclature and histological criteria.
These tumours can occur in women at any age, but peak incidence
is seen during the early 20’s. In children and adolescents,
more than 60% of ovarian neoplasms are of germ cell origin,
of which approximately 1/3 are malignant. In adults, the vast
majority of germ cell tumours are benign (nearly all mature
Dysgerminoma is the most common germ cell tumour, accounting
for 50% of all germ cell tumour cases. The yolk sac tumour
(also known as endodermal sinus tumour) is the second most
common germ cell tumour, accounting for 20% of all cases,
and is common in girls and young adults with an average age
of 19 years. Less common germ cell tumours are embryonal carcinoma,
immature teratoma, choriocarcinoma, polyembryomas, and mixed
germ cell tumours.
Embryonal carcinoma of the ovary is an extremely rare tumour
and represents only about 4 per cent of malignant ovarian
germ cell tumours . It is distinguished
from a choriocarcinoma by the absence of syncytiotrophoblastic
and cytotrophoblastic cells . Pure nongestational
choriocarcinoma of the ovary is extremely rare, as it is nearly
always admixed with other germ cell elements .
Histologically, it has the same appearance as gestational
choriocarcinoma which metastasize to the ovaries .
Mixed germ-cell tumours of the ovary contain two or more elements
of the lesions described above. In our case the combination
was that of embryonal carcinoma and choriocarcinoma.
Clinically, a substantial majority of patients with germ
cell tumours present with abdominal pain, abdominal distension
or a pelvic mass. Approximately 10 percent of patients will
present with acute abdominal pain, usually caused by rupture,
haemorrhage, or torsion of the ovarian mass. A few patients
will exhibit isosexual precocity, presumably due to HCG production
by the tumour . Embryonal carcinomas
may secrete estrogens, with the patient exhibiting symptoms
and signs of precocious pseudopuberty or irregular bleeding.
In the case of non-gestational choriocarcinoma the presence
of high HCG levels causes isosexual precocity which has been
seen to occur in about 50 percent of patients whose lesions
appear before menarche. In our case, the patient presented
with abdominal distension and irregular bleeding but there
was no evidence of precocious puberty.
Both HCG and alpha-fetoprotein are secreted by some germ
cell malignancies, therefore the presence of circulating hormones
may prove to be useful in the diagnosis and in monitoring
the response to treatment [5,6].
Ultrasonography or CT is helpful in delineating the size and
complexity of these tumours. Pre-operative staging of tumour
is possible with CT .
Microscopically a dysgerminoma component is present in 80
percent, endodermal sinus tumour in 70 percent, immature teratoma
in 53 percent, choriocarcinoma in 20 percent and embryonal
carcinoma in 16 percent. A mixture of dysgerminoma and endodermal
sinus tumour is the most common combination, accounting for
one-third of the cases . The immunohistochemical
identification of HCG in syncytiotrophoblastic cells indicates
a close relationship of embryonal carcinoma to choriocarcinoma
Treatment consists of salpingo-oophorectomy with adjunctive
chemotherapy. Chemotherapeutic regimens have evolved to combination
therapy with overall disease- free survival rates of greater
than 95 percent . Due to relatively low
toxicity and ease of treatment, chemotherapy has replaced
radiation as the preferred surgical adjuvant even when fertility
is not an issue . Second-look laparotomy
was earlier incorporated into the routine management of patients
with epithelial ovarian cancer to assess disease status after
a fixed interval of chemotherapy. However a study conducted
by Gynaecologic Oncology Group (GOG) show rather conclusively
that second-look laparatomy is not necessary in patients with
tumour completely resected initially or in those patients
with initially incompletely resected tumour that does not
contain teratoma [4,7].
In view of malignant germ cell tumours occurring almost exclusively
in young females, preservation of their ovarian function and
fertility is becoming an important, although controversial,
issue in gynaecologic oncology. A study by Zanetta et al.
confirmed that normal gonadal function and fertility are possible
after conservative surgery for ovarian germ cell malignancies,
even with adjuvant chemotherapy .
Mixed germ cell tumour (embryonal carcinoma and choriocarcinoma)
is a very rare tumour. Orientals may have a higher proportion
of non-dysgerminomatous malignant ovarian germ cell tumours
when compared to reports in the Western literature .
Careful initial surgery with adequate staging biopsies followed
by combination chemotherapy can greatly improve the prognosis
of these patients .
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Gershenson DM, Del Junco G, Copeland LJ, et al. Mixed germ cell tumors of the ovary. Obstet Gynecol 1984;64(2):200-6.
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|Received 22 June 2005; received
in revised form 17 August 2005; accepted 19 August 2005
Correspondence: Department of Biomedical Imaging (Radiology), University of Malaya Medical Centre, 59100 Kuala Lumpur, Malaysia.. Tel.: 603-79502069; Fax: 603-79581973; E-mail: email@example.com (Anushya Vijayananthan).
Please cite as: Koshy M, Vijayananthan
A, Vadiveloo V,
Malignant ovarian mixed germ cell tumour: a rare combination, Biomed Imaging Interv J 2005; 1(2):e10