Childs Nerv Syst (2002) 18:644–647

DOI 10.1007/s00381-002-0650-8 C A S E R E P O RT

Claudia M. Goetz Mixed malignant germ cell tumour

Irene Schmid
Thorsten Pietsch of the lateral ventricle in an 8-month-old girl:
Aurelia Peraud
R. J. Haas case report and review of the literature

Received: 3 July 2001 Abstract Case report: We report a Conclusion: The majority of cranial
Revised: 15 June 2002 huge intracerebral malignant germ mixed malignant GCTs affects pa-
Published online: 19 September 2002 cell tumour (GCT) which appeared tients older than 4 years of age. To
© Springer-Verlag 2002 in the lateral ventricles of an 8-month- our knowledge this is the youngest
old girl. Due to extensive tumour patient in whom an intracranial ma-
vascularisation only partial resection lignant GCT containing an embryo-
C.M. Goetz (✉) · A. Peraud was achieved. Histology revealed an nal carcinoma has been diagnosed
Department of Neurosurgery, embryonal carcinoma mixed with a and successfully treated.
Ludwig-Maximilians-Universität,
Marchioninistrasse 15, teratoma. The MIB-1 staining index
81377 Munich, Germany was >20%. Chemotherapy induced Keywords Brain neoplasm · Germ
e-mail: cgoetz@nc.med.uni-muenchen.de a marked regression of the tumour. cell tumour · Embryonal carcinoma ·
Tel.: +49-89-70952699 After chemotherapy complete resec- Infant · Treatment
Fax: +49-89-70955694
tion of the tumour remnant was easi-
I. Schmid · R.J. Haas ly achieved. Histology showed only
Paediatric Oncology, mesenchymal differentiated tumour
Ludwig-Maximilians-Universität,
Lindwurmstrasse 4, tissue and the embryonal carcinoma
80336 Munich, Germany could no longer be detected. More
T. Pietsch than 2 years after the second opera-
Department of Neuropathology, tion and 31 months after diagnosis
Universität Bonn, Bonn, Germany the child remains tumour-free.

where her mother was on holiday. She had become symptomatic

Introduction
Intracranial germ cell tumours (GCTs) have a low inci-
dence of 3.4% in Japan and this is even lower in western
countries [11]. They constitute approximately 3% of all
paediatric brain tumours [7] and arise predominantly in
children and adolescents with a median age of 16 years.
Most cranial mixed malignant GCTs affect patients older
than 4 years of age [8]. We report a huge intracerebral
malignant GCT in the lateral ventricles of an 8-month-
old girl.
Case report
In September 1999 an 8-month-old girl was presented at our hos-
pital. Ten days earlier surgery had been performed in White Russia
with irritability and vomiting and had been admitted to the local
university hospital. On CT scans a huge intraventricular contrast-
enhancing mass was visible which filled completely the right lat-
eral ventricle and partly extended to the left lateral ventricle too.
The first operation had had to be interrupted because of extreme
blood loss, but some decompression had been achieved. The bone
flap had not been reinserted. The child had recovered but had mild
left-sided hemiparesis. The family had been able to travel home.
Histology from the specimen retrieved in the first hospital re-
vealed an embryonal carcinoma. On admission to our hospital the
girl was awake and could move all her extremities but had left-
sided hemiparesis. She reacted to her mother, seemed to have nor-
mal vision and was feeding well.
MRI in our hospital showed extensive protrusion of the brain
and of the huge tumour through the craniotomy (see Fig. 1). Se-
rum markers for α-fetoprotein and β-HCG were negative. Since
the marker-status and the localisation of the tumour made the di-
agnosis of embryonal carcinoma unlikely, and the extent of the
tumour seemed to be incompatible with survival, it was decided
to operate again. Due to massive blood loss from the highly

Fig. 1 MRI scan showing con-
trast-enhancing tumour masses
in both lateral ventricles with
a big cyst located in the left
lateral ventricle
Fig. 2 MRI scan showing con-
siderable reduction in tumour
volume after four cycles of
chemotherapy
Fig. 3 MRI scan demonstrating
no tumour 14 months after ini-
tial diagnosis
vascularised tumour again only partial tumour removal was pos-
sible.
Postoperatively, the pre-existing hemiparesis worsened a little
but improved to the former state within weeks. Control MRI
showed a moderate reduction in the tumour volume and there was
no sign of dissemination along the spinal axis. Histological classi-
fication was difficult and took 16 days. Assuming the presence of
a primitive neuroectodermal tumour (PNET), chemotherapy was
started 1 week after the operation using carboplatin and VP16, but
this regimen had to be stopped due to tubulopathy. By this time,
the histology of the second operation had revealed a mixed GCT,
combining a teratoma with an embryonal carcinoma with a MIB-1
staining index >20%. Chemotherapy was continued according to
the SIOP CNS GCT 96 protocol using cisplatin, etoposide and if-
osfamide (PEI). After three cycles MRI showed remarkable
shrinkage of the tumour mass, now involving only the right lateral
ventricle (Fig. 2). A fourth cycle of PEI was administered and in
February 2000 another operation was performed. The tumour was
less vascularised and well circumscribed so that complete resec-
tion was easily achieved without much blood loss. Histology now
revealed a mesenchymal differentiated tumour with only minimal
MIB-1 staining. None of the components of the embryonal carci-
noma were still detectable. Two further cycles of PEI were admin-
istered and in October 2000 the remaining craniotomy defect was
closed using lactosorb®, a resorbable plate-system.
Since February 2000 repeated MRI scans have not revealed
any tumour regrowth (Fig. 3). The child is doing well but showing
a slight left-sided hemiparesis, a homonymous hemianopia to the
left and a minor developmental retardation of approximately
3 months. Since no tumour regrowth has yet been detected radia-
tion therapy is still withheld.
Discussion
Intracranial GCTs have a low incidence of 3.4% of all
brain tumours in Japan and this is even lower in western
countries [11]. They constitute approximately 3% of all
paediatric brain tumours [7] and arise predominantly in
children and adolescents with a median age of 16 years
[8].
They originate mainly in the pineal region, the supra-
sellar region and the third ventricle [9, 11]. Only 3–5%
of all intracranial GCTs arise in other sites; in a group of
153 patients only 3 (2%) harboured a GCT within the
lateral ventricles [12].
645
Intracranial GCTs are pathologically heterogeneous
and the nomenclature of these tumours is still not univer-
sal. According to the WHO classification system they
are subdivided into germinomas, teratomas, choriocarci-
nomas, embryonal carcinomas, endodermal sinus (yolk
sac) tumours and mixed GCTs. The four latter types are
often referred to as non-germinomatous germ cell tu-
mours (NGGCT) [12]. Embryonal carcinomas and ger-
minomas may produce low levels of AFP and ß-HCG.
Since these markers are only produced by GCTs, they
are pathognomonic if elevated [20]. Patients in early in-
fancy most often show teratomas or yolk sac tumours
[9]. Overall this group of tumours constitutes only 3% of
all GCTs. Prognosis is dependent on the extent of the tu-
mour and the histological findings [9]. Mixed GCTs in
patients younger than 2 years of age are very rarely re-
ported. In our review of the literature we were not able
to find a patient harbouring an embryonal carcinoma as
young as ours.
Treatment of GCTs has greatly changed over the last
three decades. While craniospinal irradiation was the
treatment of choice in the 1970s [15], additional chemo-
therapy is now an important part of the standard treat-
ment of NGGCTs [10, 12, 16, 18]. In particular, the in-
troduction of platinum-based chemotherapy has greatly
improved survival rates in patients with hormone secret-
ing NGGCTs [3, 4, 13, 19]. The results of the first inter-
national CNS GCT Study conducted on patients with
NGGCTs who had had chemotherapy alone were compa-
rable or better than those of patients who had had radia-
tion. There were similar relapse or progression rates for
germinomas and NGGCTs after surgery and chemothera-
py only, but a relapsed germinoma was retrievable with
irradiation while an NGGCT was not. Forty-one per cent
of the surviving patients had not had irradiation. Never-
theless, a relatively high relapse rate was observed [1]. It
was therefore proposed that after “biopsy” chemotherapy
should be administered, followed by local irradiation for
non-metastatic tumours and craniospinal irradiation for
metastatic tumours [4]. Minimising the tumour volume
646

by preoperative chemotherapy, reduces the side effects
of surgery and increases the likelihood of a complete re-
section of the tumour [5, 19]. It also decreases the viabil-
ity of tumour cells and therefore the risk of seeding
which is a major prognostic factor [9, 19].
The role of surgery in the management of pure malig-
nant NGGCTs is still being debated. Some authors advo-
cate that the diagnosis of secreting GCTs can be obtained
by radiology and CSF-markers [19] alone. In our patient
this would not have been possible, since neither tumour
localisation nor tumour appearance on MRI were typical
and the markers were not elevated. We decided to per-
form cytoreductive surgery prior to chemotherapy with
the intention of reducing the huge space-occupying mass
that was producing clinical signs of intracranial hyper-
tension and protrusion of the brain through the cranioto-
my.
In the SIOP-CNS-GCT protocol biopsy is only man-
datory for non-secreting GCTs [5]. However, whether a
simple biopsy is sufficient for diagnosis is questionable
since it provides only a small part of a potentially mixed
tumour, while prognosis is dependent on the most ma-
lignant part. Only a precise histologic characterisation
of these mixed tumours allows optimal therapeutic strat-
egies and adequate evaluation of treatment results. Be-
cause of this sampling error problem of biopsy some au-
thors recommend open surgery for tumours other than
pure germinomas and propose to aim for complete re-
section if this can be achieved with an acceptable risk
[2, 7, 9, 11, 14, 21]. Furthermore, complete surgical re-
section is the treatment of choice for pure teratomas [7,
19]. This is also true (as in our patient) of tumours of
mixed cellularity insofar as the teratoma tissue is resis-
tant to chemotherapy and radiotherapy. Recent studies
seem to indicate that radical resection as a component of
the multimodal therapy for NGGCTs can improve sur-
vival rates [8, 17, 21]. However, after chemo- and radio-
therapy surgery may be restricted to removal of the re-
sidual tumour masses. In most patients with mixed
GCTs containing teratoma a delayed tumour resection is
necessary. When operating on a previously mixed GCT
after chemotherapy (second look), some authors report-
ed that tumour specimens contained only teratoma or fi-
brous tissue [3, 6, 8, 19, 20]. This is in line with our
own experience. Because of these findings, Weiner and
Finlay [20] recommend the surgical resection of all re-
sidual masses that were still present after the initial che-
motherapy in patients with absent or markedly reduced
tumour markers.
Matsutani et al. [12] reported 1 patient with an
embryonal carcinoma who, like our patient, was treated
with surgery and chemotherapy only and survived
for more than 10 years. They also reported that
some of the patients with a poor prognosis (pure or
mixed choriocarcinomas, embryonal carcinomas or yolk
sac tumours) showed a rapid response to chemothera-
py, like the infant described in our paper. However,
a longer follow-up revealed recurrences mainly at the
primary tumour site. They therefore suggested more
aggressive chemotherapy followed by focused radia-
tion.
Conclusion
In conclusion, the majority of NGGCTs has to be treat-
ed using an interdisciplinary approach but surgery nev-
ertheless has a distinct role in this treatment. The opti-
mal treatment is still being debated. In very young chil-
dren, only chemotherapy and surgery are acceptable
treatment options. Chemotherapy may in some cases
change the tumour’s characteristics and thus render a
non-resectable tumour resectable. By using all treat-
ment options in the right setting complete tumour re-
mission can be achieved even in a patient with an ini-
tially poor prognosis.

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