Keywords
germ cell - tumor - yolk sac tumor - temporal lobe
Introduction
Central nervous system (CNS) germ cell tumors account for 2 to 3% of the primary intracranial
tumors, and are usually located in the midline (in the pineal or sellar regions).[1] The yolk sac tumor is a relatively rare germ cell tumor.[2]
[3] The occurrence of this type of tumor outside the midline is an exception, with very
few cases described in the literature.[1]
[2]
[4]
[5]
[6] When they occur in atypical locations, they are usually lesions with a cystic component
and poor prognosis.[5]
Case Report
A 32-year-old male patient, who sought the emergency department with a headache with
2 weeks of evolution and papillary stasis. No other focal neurological signs were
observed.
The imaging investigation revealed a right temporal intra-axial lesion with heterogeneous
contrast uptake and a cystic/necrotic area ([Fig. 1]). The hypothesis of the diagnosis was high-grade glioma (HGG).
Fig. 1 Preoperative magnetic resonance imaging revealing right temporal lesion, hypointense
in T1 (a), with heterogeneous signal in T2 (b), heterogeneous contrast uptake and
cystic/necrotic area (c, d), with mass effect on the structures of the midline.
The patient underwent a right frontotemporal craniotomy with a temporal lobectomy
encompassing the lesion in its entirety ([Fig. 2]). The lesion had a hard, vascularized consistency, and a cystic area of yellowish
content, macroscopically similar to an HGG.
Fig. 2 Postoperative magnetic resonance imaging (axial, T1, with gadolinium) revealing right
temporal lobectomy with absence of anomalous contrast uptake.
Clinically, the patient improved postoperatively, without headaches or focal deficits.
The neuropathological examination revealed a germ cell tumor forming, in some places,
tubular structures composed of cells with prominent nuclei, and numerous mitoses were
observed. The immunocytochemical examination was positive for both α-fetoprotein and
glypican 3,([Fig. 3]), and negative for glial fibrillary acidic protein (GFAP), human chorionic gonadotropin
(HCG), and epithelial markers. In this sense, a systemic investigation including a
positron emission tomography (PET) scan was performed to investigate a possible primary
tumor (assuming that, from the location of the brain lesion, it would be metastatic).
The investigation was negative, and no other tumor was found. The study of the neuraxis
also revealed no other lesions.
Fig. 3 Hematoxylin eosin (HE) histology (a) demonstrating neoplasia formed by lobules of
nucleolated round nuclei, with numerous mitoses (arrows), positive immunocytochemistry
for alpha-fetoprotein (b) and glypican 3 (c).
The patient was directed to four cycles of chemotherapy – ifosfamide + cisplatin + etoposide
(ICE), which would be followed by holocranial brain radiotherapy.
At 3 months, during the third cycle of chemotherapy, a magnetic resonance imaging
(MRI) exam revealed intracranial meningeal metastases. At this time, the patient remained
clinically stable. A decision was made to continue with the fourth cycle of chemotherapy
and subsequent radiotherapy. At an MRI exam performed at 5 months, the patient maintained
the metastases already known ([Fig. 4]). Three weeks after this examination, already under radiotherapy, there was an important
neurological deterioration, revealing a marked growth of metastases in the computerized
axial tomography (CAT) scan, as well as new lesions ([Fig. 5]). Due to the lack of response to the treatment, the radiotherapy was discontinued.
The patient deteriorated rapidly to a comatose state, dying 3 weeks later, ∼ 7 months
after surgery.
Fig. 4 Magnetic resonance imaging (axial, T1, with contrast) at 5 months with evidence of
metastasis.
Fig. 5 Computed axial tomography (3 weeks after magnetic resonance imaging [[Fig. 3]] under radiotherapy) revealing marked lesion growth and de novo lesions.
Discussion
Germ cell tumors are divided into two major groups: germ cell and non-germ cell tumors
(yolk sac tumor, choriocarcinoma, embryonal carcinomas, and teratomas).[7] The latter group has a worse prognosis.[6]
[7]
In the presence of a tumor located in the midline, in a child or young adult, the
hypothesis of a germ cell tumor should be considered. A search for tumor markers (α-fetoprotein
and β-HCG) in the blood and/or in the cerebrospinal fluid (CSF) should be performed.
Germinomas are the most common tumors of this group; and, in this case, the markers
are usually negative, and the diagnosis requires histological confirmation through
biopsy.[7] Since this type of tumor has an excellent response to radiotherapy, with long-term
regression rates of ∼ 90%, excision surgery does not lead to an improvement in the
outcome.[7]
On the other hand, the positivity of α-fetoprotein labeling will determine the diagnosis
of yolk sac tumor without the need of histological confirmation for therapeutic orientation.[7] In the case described in the present report, this hypothesis was never raised due
to the location of the lesion, which is why this study was not performed preoperatively.
The temporal location of a yolk sac tumor is extremely rare. To our knowledge, there
are 19 cases reported in the literature[6]
[8] on the occurrence of this tumor outside the midline, with only 4 located in the
cerebral lobes – the remaining reported cases occurred in the lateral ventricles,
in the fourth ventricle, in the thalamus/basal ganglia, in the cerebellum, or in the
rachis)[6]
[8] ([Table 1]).
Table 1
|
Site
|
Author
|
Gender
|
Age (years)
|
Treatment
|
Survival (months)
|
|
Spine
|
Kurisaka et al.
|
Female
|
1
|
Surgery + CT
|
8b
|
|
Spine
|
Kan et al.
|
Female
|
25
|
Surgery + RT + CT
|
22b
|
|
Cerebellum
|
Takeda et al.
|
Male
|
4
|
Surgery + RT
|
8a
|
|
Cerebellum
|
Tajika et al.
|
Male
|
3
|
Surgery + CT
|
4a
|
|
Cerebellum
|
Tsukamoto et al.
|
Male
|
3
|
Surgery + RT + CT
|
18a
|
|
Cerebellum
|
Nakase et al.
|
Male
|
5
|
Surgery + CT
|
12a
|
|
Cerebellum
|
Wada et al.
|
Male
|
6
|
Surgery + CT
|
5b
|
|
Cerebellum
|
Cheon et al.
|
Male
|
3
|
Surgery + CT
|
48a
|
|
Basal ganglia
|
Masuzawa et al.
|
Male
|
10
|
Surgery + RT
|
NAb
|
|
Basal ganglia
|
Oshita et al.
|
Female
|
8
|
Surgery + RT + CT
|
NAb
|
|
Basal ganglia
|
Wang et al.
|
Female
|
7
|
Surgery + RT + CT
|
NAb
|
|
Lateral ventricle
|
Murovic et al.
|
Female
|
2
|
Surgery + RT
|
42a
|
|
Lateral ventricle
|
Tsugu et al.
|
Female
|
13
|
Surgery + RT + CT
|
7b
|
|
Fourth ventricle
|
Nakagawa et al.
|
Male
|
18
|
Surgery + RT
|
5a
|
|
Frontal lobe
|
Sugawara et al.
|
Female
|
18
|
Surgery + RT + CT
|
3a
|
|
Frontal lobe
|
Netalkar et al.
|
Female
|
15
|
Surgery + CT
|
36a
|
|
Frontal lobe
|
Honda et al.
|
Male
|
1
|
Surgery + CT
|
9b
|
|
Middle fossa + orbit
|
Dragan et al.
|
NA
|
15
|
Surgery + CT
|
5a
|
|
Temporoparietal lobe
|
Abdennebi et al.
|
Female
|
1
|
Surgery + RT
|
NAb
|
|
Temporal lobe
|
Present case
|
Male
|
32
|
Surgery + CT + RT
|
7b
|
The definitive diagnosis and correct orientation of a case like this requires an exhaustive
study for the exclusion of an extracerebral primary tumor. In our case, this study
included a thoracoabdominopelvic CAT scan, a testicular echography, and a PET scan,
which were negative.
Germinomas are undifferentiated and aggressive tumors, with a poor response to the
complementary treatment. Given the rarity of non-germ cell germ cell tumors histologies,
in literature reviews of prognosis and survival these are often grouped in the same
category,[7] with a 45% survival rate at 2 years for this subgroup of tumors. From the 19 cases
described outside the midline[1]
[6] at the time of the respective publications, 4 patients had died in less than 1 year
(in 4 cases, the survival was not described). Regarding the modalities of complementary
treatment, 12 patients from the 19 cases were submitted to chemotherapy programs (5
in conjunction with radiotherapy).[6]
[8] Two patients underwent the same scheme of the case presented here. Three patients
received vinblastine + cisplatin + bleomycin. Two patients received carboplatin + etoposide + bleomycin.
One patient received vincristine + cisplatin + bleomycin. One patient received etoposide + cisplatin + bleomycin.
One patient received carboplatin + vinblastine + etoposide. One patient received intrathecal
methotrexate and cytosine + carboplatin + bleomycin. And one patient received vinblastine + bleomycin + cisplatin + etoposide.[6]
Conclusion
The tumor of the yolk sac of the CNS is a germ cell tumor with aggressive characteristics
and poor prognosis. The present case reinforces the notion that, although rare, this
tumor may occur outside the midline. Having no imaging characteristics that clearly
distinguish it from other primary malignant CNS tumors, namely HGGs, it should be
maintained as a diagnostic hypothesis in young individuals, since the therapeutic
and prognostic orientation are markedly different for this type of tumor.
