Arch Gynecol Obstet (2009) 280:803806
DOI 10.1007/s00404-009-0977-4
C A S E RE P O RT
Management of a pregnancy complicated by yolk sac tumor
I. PaWlis D. Haidopoulos A. Rodolakis G. Vlachos
Z. Voulgaris M. Sotiropoulou A. Antsaklis
Received: 10 July 2008 / Accepted: 30 January 2009 / Published online: 21 February 2009
Springer-Verlag 2009
Abstract
Background The management of ovarian cancer during
pregnancy represents a major challenge and requires close
multidisciplinary team approach.
Case A 35-year-old pregnant woman with a yolk sac
tumor underwent left salpingo-oophorectomy at 25 weeks
of gestation. Chemotherapy was deferred to the end of the
pregnancy owing to concerns for potential fetal risks.
Alpha-feto protein level was used to monitor the underlying
disease activity. The patient underwent exploratory laparot-
omy with cesarean section followed by total hysterectomy,
omentectomy, right salpingooophorectomy, pelvic, and
para-aortic lymphadenectomies at 32 weeks of gestation.
She received four postoperative courses of chemotherapy
(cisplatin, etoposide, and peplomycin). Currently, mother
and child are doing well 6 months after the last chemother-
apy cycle.
Conclusion In a case of yolk sac tumor in the second tri-
mester of pregnancy, radical surgery combined with elec-
tive caesarian section followed by chemotherapy could
achieve remission and rescue of fetus. However, the treat-
ment needs to be individualized as there is lack of evidence.
Keywords Yolk sac tumor Pregnancy AFP Cisplatin
Etoposide Peplomycin
I. PaWlis (&) D. Haidopoulos A. Rodolakis G. Vlachos
Z. Voulgaris M. Sotiropoulou A. Antsaklis
1st Department of Obstetrics and Gynecology,
Gynecologic Oncology Unit, Alexandra Hospital,
University of Athens, Athens, Greece
e-mail: johnpaWlis@hotmail.com
Introduction
Ovarian cancer is the second most frequent gynecological
cancer complicating pregnancy [1]. When a malignant
ovarian tumor is diagnosed during gestation, it is adenocar-
cinoma in 35%, borderline malignant tumor in 30% and
germ-cell/sex cord stromal tumor (mostly dysgerminomas)
in 35% of cases [2]. The yolk sac tumor is a malignant
germ-cell neoplasm arising from multipotential embryonal
stem cells with diVerent ion toward yolk sac and vitelline
structures [3]. Accounting for 1% of ovarian malignancies
overall, it is rare but highly malignant tumor, occurring pri-
marily in children and young women, whereas its incidence
in pregnancy is exceptionally low.
The detection of malignancy during pregnancy often
requires diYcult decision regarding maternal therapy and
the side eVects of the treatment to the unborn child. The
optimal management of pregnant patients with ovarian can-
cer should aim to beneWt the mothers life and protect the
fetus from the harmful eVects of cancer treatment [4, 5].
Surgical management during pregnancy is similar to non-
pregnant patients and consists of unilateral salpingo-oopho-
rectomy in the initial stages of the disease. Prognosis seems
to be similar if appropriate treatment is conducted.
Malignant germ-cell tumor of the ovary is extremely
sensitive to chemotherapy. Prognosis has markedly
improved with the concomitant use of bleomycin, etopo-
side, and cisplatin. However, the decision to start cytotoxic
therapy in a pregnant patient remains a dilemma. Almost all
chemotherapy agents can cross the placenta and cause tera-
togenesis. In addition, no comparable data are available to
determine the long-term eVects on individuals who have
been exposed to chemotherapy in uterus. Therefore, it is
imperative that such patients are under the care of a multi-
disciplinary team that includes a high-risk obstetrician, a
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804 Arch Gynecol Obstet (2009) 280:803806

gynecological oncologist, and a medical oncologist special-

ized in gynecological cancers.
With this case, we are reporting the management of
a yolk sac tumor detected in the second trimester of
pregnancy.

Case report

A 35-year-old woman that was under our care with a his-

tory of primary infertility became pregnant following
several attempts at IVF. She underwent an ultrasound
scan because of abdominal pain at 24 weeks of gesta-
tion. Ultrasound identiWed a lesion arising from the left
adnexal, measuring 17 cm that appeared to be predomi-
nantly cystic with solid parts and papillary formations. Fig. 1 Tumor with characteristic SchillerDuval bodies and polyve-
sicular pattern (H&E 100)
These features were highly suspicious of malignancy
and as per our departments policy we measured the fol-
lowing tumor markers: AFP, CA 199, CEA, CA 125.
These were all normal apart from a markedly elevated
maternal serum alpha-feto-protein (AFP) to 247 ng/ml.
Subsequent detailed fetal scanning was normal and
excluded fetal abnormality as the cause of the abnormal
AFP level.
At 25 weeks of gestation, she underwent laparotomy
conWrming the presence of a left ovarian cyst with maxi-
mum diameter 17 cm. During the procedure, the wall of the
cyst was ruptured and a gelatinous yellow Xuid came out. A
left salpingo-oophorectomy and partial omentectomy was
performed.
The cut section showed a pattern of solid and cystic Fig. 2 Hepatoid pattern with hyaline bodies. Tumor cells with moder-
areas with regions of hemorrhage and necrosis, and was ate atypia and mitotic Wgures (H&E 400)
yellow-tan in color. The Xuid present in the cystic spaces
was gelatinous. Microscopically, the sections exhibited his- Unfortunately, the levels of AFP which had declined to
tological appearances typical of yolk sac tumor. Many 30 ng/ml a week after the surgery elevated to 500 ng/ml
endodermal sinus patterns were present including reticular, 5 weeks after the operation. As the patient had reached
papillary, solid, polyvesicular vitelline, and polyembryonal 32 weeks of gestation and the fetus was considered viable it
histology. Numerous SchillerDuval bodies were also pres- was decided to proceed to an elective caesarian section
ent (Figs. 1, 2). The tumor cell components were positive combined with radical surgery for the underlying cancer.
for AFP. The omentum showed no metastatic lesions. The A healthy baby was delivered by elective cesarean sec-
Wnal histopathological diagnosis was an ovarian yolk sac tion at 32 weeks. The male infant was 1,335 g with an
tumor and the patient was staged as having FIGO stage Ic Apgar Score of 9 at 1 min and 10 at 5 min. The placenta
(at least) disease. appeared normal at the time of delivery. During the section,
Alpha-feto protein levels repeated after initial surgery implantations with diameter 12 cm were found on the
declined substantially. Following extensive counseling of abdominal peritoneum and on the omentum. Adhesions to
the patient and partner by our multidisciplinary team, che- the sigmoid were also noted. Possible metastatic lesions
motherapy was deferred to the postpartum period in view of were also found in the liver with diameter 23 cm. Total
concerns for potential fetal risks. She was managed as a hysterectomy, omentectomy, right salpingo-oophorec-
high-risk pregnancy performing antenatal ultrasound scans tomy, pelvic, and para-aortic lymphadenectomies were car-
every 2 weeks that showed a small for gestational age fetus ried out. Residual disease was documented at surgery and
but with normal anatomical structures and movements. A Wnal histological examination conWrmed a malignant yolk
serum AFP level was taken at the time of the scans in order sac tumor. The placenta was tumor free. This was consis-
to detect cancer recurrence. tent with stage IV disease according to FIGO classiWcation.

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Arch Gynecol Obstet (2009) 280:803806
She then underwent four courses of platinum, etoposide,
and bleomycin and her serum AFP monitored every month
afterwards rapidly declined to undetectable levels. The
mother and child are doing well 6 months after the last
cycle of chemotherapy.
Discussion
Yolk sac tumors, unlike most ovarian malignancies, have
been known to be highly responsive to combined chemo-
therapy agents. This is the rationale behind using chemo-
therapy after surgical resection in the initial stages of the
disease or as Wrst line in more advanced cases.
However, the use of such agents during pregnancy has
not been validated. Pregnancy aVects various physiological
parameters and there is currently no available evidence on
the necessary therapeutic doses of chemotherapy during
this period [6]. Current experience has shown increased ter-
atogenicity during the Wrst trimester [79] but reports on
pregnancy outcomes during second and third trimester have
been more uncertain [10]. Although normal pregnancy out-
comes have been suggested from isolated reports [11],
plethora of adverse fetal outcomes have been reported in
the literature [10, 1214]. Furthermore, as yolk sac tumors
are particularly rare during pregnancy there is limited
expertise and certainly no consensus among clinicians on
their optimal management.
In our case, we had to deal with a precious pregnancy.
Our advanced aged patient gets pregnant after years of
infertility and only after IVF treatment. The patient and her
family strongly desired continuation of the pregnancy. In
view of the above, decision on further management was
taken after careful review of the available evidence and
consideration of the patients wishes.
In our initial assessment, the size of the ovarian mass as
well as its suspicious radiological features made surgery
essential and, therefore, we performed salpingo-oophorec-
tomy and partial omentectomy at 25 weeks of gestation.
Much eVort was taken in order to achieve a correct staging
and prognostic characterization and, more important, the
most eVective tumor debulking compatible with preserva-
tion of pregnancy. Pregnancy was not aVected during or
after surgery.
The progress of the disease was monitored using the lev-
els of serum AFP. Serum AFP is a useful marker for both
the diagnosis and post treatment monitoring in the cases of
yolk sac tumors. Elevated level of serum AFP is found in
all patients with malignant tumors containing yolk sac com-
ponents at diagnosis [15, 16]. Decreasing level of postoper-
ative serum AFP is an eVective indicator to determine
whether residual disease remains or not after surgery [17,
18]. Alterations associated with the gravid state make the
805
interpretation of tumor markers, including AFP, diYcult.
During normal pregnancy, Wrst the yolk sac then the fetal
liver and gastrointestinal tract produces AFP. Maternal
serum AFP levels are used to screen for certain fetal abnor-
malities, particularly neural tube defects and trisomy 21.
Nonetheless, substantially elevated levels are associated
with endodermal sinus tumors. Outcome of many cases
support that a germ-cell tumor of either gonadal or extrago-
nadal origin should be considered as a diagnostic alterna-
tive in pregnant women with elevated serum AFP in
the absence of any fetal malformation or maternal disease
[11, 14]. In our patient, tumor recurrence was presumed fol-
lowed an elevated AFP to 500 ng/ml, since major fetal
anomaly was excluded by detailed ultrasound scanning.
Exploratory laparotomy with cesarean section followed
by total hysterectomy, omentectomy, right salpingo-oopho-
rectomy, pelvic and para-aortic lymphadenectomies were
performed at 32 weeks of gestation. After termination of
pregnancy, the patient underwent four courses of chemo-
therapy and routine follow-up procedures were started. Six
months later, there was no evidence of recurrence clinically
or radiologically and patients serum AFP levels remained
undetectable. The mother didnt breastfeed, since breast-
feeding during cytotoxic chemotherapy has been discour-
aged in general [19].
In conclusion, our case suggests that unilateral salpingo-
oophorectomy and surgical staging, without initial combi-
nation chemotherapy could be considered in a pregnant
woman with a yolk sack tumor diagnosed during the second
trimester of pregnancy, although it may not be the standard
management in such patients. Chemotherapy during preg-
nancy requires consideration of the eVects on both the
mother and fetus. A multidisciplinary team should be
responsible for the management .The risks and beneWts
have to be discussed with caution, considering the limited
data on the short and long-term infant sequelae of chemo-
therapy exposure in the uterus.
ConXict of interest statement None.
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