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Brain Tumor Pathology ISSN 1433-7398 Brain Tumor PatholDOI 10.1007/s10014-012-0110-4
Brain stem gliomas: a clinicopathologicalstudy from a single cancer center
Maysa Al-Hussaini, Usama Al-Jumaily,Maisa Swaidan, Awni Musharbash &Sameh Hashem
1 23
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ORIGINAL ARTICLE
Brain stem gliomas: a clinicopathological study from a singlecancer center
Maysa Al-Hussaini • Usama Al-Jumaily •
Maisa Swaidan • Awni Musharbash •
Sameh Hashem
Received: 12 March 2012 / Accepted: 11 June 2012
� The Japan Society of Brain Tumor Pathology 2012
Abstract Brain stem gliomas (BSG) are rare tumors
occurring predominantly in childhood. They are mostly of
astrocytic origin and are divided into infiltrative versus
circumscribed types, with different prognoses. The diag-
nosis is mainly based on MRI findings, and biopsy is rarely
performed. This is a retrospective study of BSG with
available biopsies diagnosed at our center over 6-year
period. Fifteen cases were identified, with a predominance
of females. The median age was 7 years, and the mean
duration of symptoms was\6 weeks in 58.3 % (n = 7) of
cases. MRI was typical of diffuse pontine gliomas in
64.3 % (n = 9) of cases. Radiotherapy was the commonest
modality of treatment, and the median overall survival was
21.7 months. Twelve cases were consistent with infiltrative
astrocytoma of various grades (2 grade II, 7 grade III and 3
grade IV). Entrapped normal neurons and mitosis were the
commonest findings indicating infiltrative growth and high
grade, respectively, and those correlated significantly with
immunostaining for neurofilament protein and Ki-67 of
C3 %. Overall survival correlated only with the duration of
symptoms and tumor grade on biopsies. A limited panel of
immunostains might be useful in undetermined cases to
decide on the growth pattern and grade.
Keywords Brain stem glioma � Biopsy �Immunohistochemistry � Diffuse pontine glioma �Pilocytic astrocytoma
Introduction
Brain stem gliomas (BSG) are rare tumors. They are mostly
seen in childhood where they account for 10–20 % of brain
tumors [1]. Classification depends primarily on radiologi-
cal assessment of the location and pattern of growth [1–3].
Diffuse pontine glioma (DPG) is the most common type
accounting for 70 % of cases. MRI typically reveals diffuse
enlargement of the pons with encasement of at least one
half to two-thirds of the basilar artery. Exophytic tumors
on the other hand are seen primarily in the mid brain or
the medulla oblongata, and are characterized by a cystic
component that projects posteriorly into the ventricles with
an enhancing solid component. This radiological classifi-
cation correlates well with the tumor histological type and
grade [4, 5]. Fibrillary infiltrative astrocytoma represents
the majority of DPGs, where high grade gliomas of ana-
plastic astrocytoma and glioblastoma multiforme types
predominate [6], whereas exophytic tumors are mostly
grade I pilocytic astrocytoma [4]. The treatment modality,
outcome and prognosis differ drastically between both
groups [7]. DPGs are associated with a dismal outcome,
M. Al-Hussaini (&)
Department of Pathology,
King Hussein Cancer Center (KHCC), Queen Rania Street,
P.O. Box 1269, Al-Jubeiha, Amman 11941, Jordan
e-mail: [email protected]
U. Al-Jumaily
Department of Pediatric Oncology,
King Hussein Cancer Center (KHCC), Amman, Jordan
M. Swaidan
Department of Radiology,
King Hussein Cancer Center (KHCC), Amman, Jordan
A. Musharbash
Department of Surgery,
King Hussein Cancer Center (KHCC), Amman, Jordan
S. Hashem
Department of Radiation Oncology,
King Hussein Cancer Center (KHCC), Amman, Jordan
123
Brain Tumor Pathol
DOI 10.1007/s10014-012-0110-4
Author's personal copy
with 10 % survival at 1 year. Palliation radiotherapy and
disclosure of poor prognosis are offered once the diagnosis
has been made [8]. In contrast, exophytic tumors are
associated with excellent outcomes, with 5-year survival of
90 %. Surgical excision followed by conservative follow-
up is the treatment of choice [9].
Pre-treatment biopsy is rarely performed in cases of
BSG [10]. Most clinico-pathological correlations were
originally made on post-mortem specimens [11]. An
atypical radiological appearance where the diagnosis, and
thus management and prognosis, cannot be determined
with certainty remains the strongest indication for biopsy
[12, 13]. Stereotactic biopsy has replaced open craniotomy
in many neurosurgical approaches. While this is associated
with less morbidity to patients [14], specimens sent to the
pathologists are considerably smaller in size, creating
diagnostic challenges.
Immunohistochemistry has been established as an
adjunct in supporting the diagnosis and grading of brain
tumors [15, 16]. Neurofilament protein is a commonly
used marker in neuro-pathology, useful in determining
the circumscribed versus the infiltrative growth pattern.
Pilocytic astrocytoma tends to be circumscribed with few
NFP-positive fibers seen mainly at the periphery of the
tumor. In contrast, tumor cells infiltrate extensively in
between pre-existing fibers in infiltrative astrocytic tumors
of all grades. Ki-67 is used to assess the proliferative
potential in brain tumors, and in conjunction with other
features, especially mitosis can help in guiding the grad-
ing of tumors. Cutoff values to separate low- from high-
grade tumors are variable, but low-grade tumors tend to
show a proliferative index of \3 %, while high-grade
glial tumors are diagnosed when 10 % or more of tumor
cells are positive [16]. TP53 is a tumor suppressor gene,
and positive immunostaining is detected in many high-
grade brain tumors, especially secondary glioblastoma,
medulloblastoma with anaplasia and anaplastic meningi-
oma. In addition, it is used to differentiate pilocytic from
low-grade infiltrative fibrillary astrocytoma, being con-
sistently negative in the former.
We aim at describing our experience with cases of BSG
in which pre-treatment biopsies were obtained. The clini-
cal, radiological and pathological findings are described.
The value of adding a limited panel of immunohisto-
chemical stains, namely NFP, Ki-67 and P53, in reaching
the final diagnosis in equivocal cases is described.
Materials and methods
This is a retrospective study. After obtaining approval from
the KHCC Institutional Review Board (which works in
accordance with Declaration of Helsinki and ICH-GCP),
files from cases diagnosed with brain stem glioma over a
6-year period (2003–2009) were reviewed, and cases with
available pathological diagnoses were retrieved. The clin-
ical as well as radiological findings were collected. The
duration of the symptoms prior to presentation was
obtained, and a cutoff of 6 weeks was used to separate
cases with short- versus long-term presentations. Radio-
logical findings were described as typical when brain MRI
showed evidence of diffuse expansion of the pons with
encasement of at least two thirds of the basilar artery with
or without enhancement; otherwise, radiology was con-
sidered atypical. The operative approach for obtaining the
biopsy, the site targeted, as well as any further surgical
resection was recorded when available. Modalities of
treatment offered including radiotherapy and/or chemo-
therapy were collected. The outcome of the patient was
determined as dead versus alive at the time of collection of
data. The date of death of the patient or last follow-up/
clinic visit was recorded, and overall survival was calcu-
lated. Details that might disclose the identity of the patients
were omitted, and only coded data were used for analysis.
Review of the available H&E slides was performed.
Pathological features were assessed semi-quantitatively.
The degree of cellularity and pleomorphism was evaluated
on a scale from 1 to 3 (1 = mild, 2 = moderate, 3 =
marked). Entrapped neurons, mitosis, apoptosis, vascular
proliferation, necrosis, Rosenthal fibers (RF) and eosino-
philic granular bodies (EGBs) were assessed on a two-tier
scale (present vs. absent). The presence of entrapped nor-
mal-looking neurons signifies an infiltrative growth pattern,
while their absence can be related either to sampling in an
infiltrative glioma or alternatively the circumscribed nature
of the tumor. Mitosis was assessed as present when C1
mitosis was identified in any biopsy fragment, which was
consistent with the diagnosis of anaplastic astrocytoma in
infiltrative tumors and absent when a search of all available
slide(s) failed to reveal any. Apoptosis was considered
present if C1 apoptotic bodies were seen in any high-power
field (HPF). Vascular proliferation in the form of glom-
eruloid blood vessels and necrosis, whether palisading or
not, were assessed as absent versus present. The presence
or absence of Rosenthal fibers and EGBs was recorded in
all cases.
Immunohistochemistry staining for three markers, neu-
rofilament protein (clone2F11, Ventana ready to use, with
heat retrieval using EDTA buffer), Ki-67 (DAKO; clone
M1B-1, 1:50 dilution with heat retrieval using EDTA
buffer) and P53 (clone D07, Venetana, ready to use, with
heat retrieval using EDTA buffer) was performed using
automated Ventana immunostainer. Positive and negative
controls were run for each antibody. Positivity was evalu-
ated semi-quantitatively. The tumors were considered
infiltrative only if neurofilament protein was diffusely
Brain Tumor Pathol
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positive in all biopsies evaluated in any single case, while
occasional positive NFP fibers or a totally negative NFP
staining could be related to circumscribed tumor growth
or sampling the middle zone of an infiltrative tumor. The
Ki-67 proliferative index cutoff of C3 % was used to
separate high- from low-grade infiltrative astrocytomas.
P53 was considered positive when strong nuclear staining
was seen in more than 50 % of tumor cells.
Statistical analysis was performed using SAS version
9.1 (SAS Institute Inc, Cary, NC, USA). Descriptive sta-
tistics including the mean, median, and SD were calcu-
lated. In addition, the counts and percentages were also
estimated. Fisher’s exact test was used to compare among
several factors and the pathological results. Kaplan-Meier
survival curves were used to describe the outcome in all
patients. Log rank was used to compare between survival
curves. The P value was considered significant if B5 %.
Results
A total of 15 cases were indentified, 12 females and 3
males, with a median age of 7.0 years (2.1–29.8 years),
representing 42 % of all BSG cases treated at our center.
Nine (60 %) patients were Jordanian. Seven (46.7 %)
patients were initially biopsied and diagnosed outside our
center, then referred for further management. These were
biopsied using MRI-guided stereotactic biopsy where areas
of enhancements corresponding to high-grade tumor areas
were targeted; otherwise, the most peripheral area of the
tumor was targeted. Cases biopsied at our center were
approached through endoscopic biopsies from parts of the
lesion bulging into the third ventricle. The mean duration
of symptoms was \6 weeks in seven (54.5 %) patients
with available data. The most common presenting symp-
toms were cranial nerve palsies (n = 12; 80 %), upper
limb/lower limb weakness (n = 10; 66.7 %), ataxic gait
(n = 9; 60 %), headache (n = 7; 46.7 %), and nausea and
vomiting (n = 6; 43.1 %). Initial and follow-up MRIs were
available for 14 patients to determine the primary site and
growth pattern of the tumor. The tumor was located in the
pons in ten (71.4 %) patients, the mid brain in two
(14.3 %) and the medulla oblongata in the remaining two
(14.3 %) patients. MRI was not available in a single patient
for evaluation of the exact site. MRI was typical of DPG in
nine patients (64.3 %), while the findings were considered
atypical in five patients (35.7 %), including one pontine
case. Radiotherapy only was the most common modality of
treatment offered to nine (64.3 %) patients, chemotherapy
alone was offered to two (14.3 %), and combination
chemo-radiotherapy was offered to a single (7.1 %)
patient. All radiotherapy-treated patients but one (case no.
10) received a total dose of 54 Gy (1.8 Gy daily/30
fractions, 5 days a week). Families of two patients
(14.3 %) with pontine gliomas elected no treatment.
Debulking surgeries were offered to three patients, two
pilocytic astrocytoma cases (case nos. 1 and 2) and a single
glioblastoma case (case no. 15). Table 1 summarizes
patients’ demographics, clinical and radiological findings,
treatment modalities and outcomes.
Pathologically, the diagnosis in 12 (80 %) patients was
consistent with infiltrative fibrillary astrocytoma, including
2 (13.3 %) grade II fibrillary astrocytomas, 7 (46.7 %)
grade III anaplastic astrocytomas and 3 (20.0 %) grade IV
glioblastomas. Three (20.0 %) patients were diagnosed
with grade I pilocytic astrocytoma. Increased cellularity
was seen in seven (46.7 %) cases, all of high grade
(AA = 5, GBM = 2), while marked pleomorphism was
seen in five (33.3 %) cases (AA = 4, GBM = 1). Entrap-
ped neurons were identified in eight (53.3 %) infiltrative
astrocytoma cases (FA = 2, AA = 5, GBM = 1). The rest
of the cases showed no neurons (PA = 3, AA = 2,
GBM = 2). Mitosis was the most common high-grade
feature detected in eight (53.0 %) infiltrative astrocyto-
mas, but not in pilocytic astrocytoma cases. Microvascu-
lar proliferation was detected in six (40.0 %) cases
(GBM = 3, PA = 3), and necrosis was seen only in a
single (6.7 %) glioblastoma case. Apoptosis was detected
in all infiltrative astrocytoma cases but one (n = 11;
73.3 %). Rosenthal fibers were detected only in pilocytic
astrocytoma (3 cases). EGBs were not detected in any of
the cases.
Additional unstained slides/paraffin blocks to perform
immunostains were available in only 11 cases. All cases
with no additional slides/blocks were high-grade gliomas
where slides were only submitted for the initial diagnosis
from referring centers. NFP was diffusely positive in five
(45.5 %) cases, all of infiltrative astrocytoma type, while it
was totally negative or seen as occasional fibers within the
tumors in six (54.4 %) cases (PA = 3, FA = 1, AA = 1,
GMB = 1). Ki-67 was C3 % in eight (72.7 %) cases,
including two pilocytic astrocytoma cases and\3 % in the
remaining three cases (PA = 1, FA = 2). P53 was positive
in only two (18.2 %) high-grade glioma cases (AA = 1,
GBM = 1). Table 2 summaries the most important path-
ological and immunohistochemical findings.
When comparing high-grade (AA = 7, GBM = 3)
versus low-grade (PA = 3, FA = 2) tumor groups, patients
tended to be younger (median 74 vs. 100 months), showed
more predominance of females (90 vs. 60 %), a shorter
median duration of presenting symptoms (3.5 vs. 6 weeks),
and fewer alive patients (2/6 vs. 4/4), respectively, but
none of the features reached statistical significance. Fig-
ures 1 and 2 demonstrate radiological findings (Figs. 1a,
2a), routine hematoxylin and eosin-stained slides (Figs. 1b,
2b), and immunostains for NFP (Figs. 1c, 2c) and Ki-67
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Table 1 Patients’ demographics, clinical characteristics, radiological findings and outcomes
No. Sex Age
(months)
Symptoms
(weeks)
Location MRI Surgery Pathology RTX
(Gy)
CTX Status OS
(months)
1 F 63 4 Cervico-
medullary
Atypical Bx and excision of
cyst
PA No Carbo/
VCR
Alive AWD
2 M 98 6 Pons and
midbrain
Atypical Bx and subtotal
excision
PA No No Alive AWD
3 F 100.3 2 Tectum/
midbrain
Atypical Bx PA 54 Carbo/
VCR
NA NA
4 F 132 8 Pons Typical Bx* FA/grade
II
54 No Alive AWD
5 M 357 78 Medulla
oblongata
Atypical Bx FA/grade
II
54 No Alive AWD
6 F 25 36 Pons Typical Bx AA Nob Carbo/
VCR
NA NA
7 F 50 16 Pons Typical Bx* AA 54 No Alive AWD
8 F 62 2 Pons Typical Bx* AA 54 No Dead 4.7
9 F 64.9 3 Pons Typical Bx* AA 54 No Dead 21.7
10 M 81.1 4 Pons Typical Bx* AA 10.8c No Dead 2.1
11 F 225 12 Midbrain Atypical Bx* AA 40 No Alive AWD
12 F 240 NA Brain stema NA Bx* AA NA NA NA NA
13 F 67 NA Pons Typical Bx GBM No No Dead 1
14 F 83.6 3 Pons Typical Bx* GBM 54 No Dead 21
15 F 171 2 Pons Typical Bx and debulking GBM 54 No Dead 3
AA anaplastic astrocytoma, AWD alive with disease, Bx biopsy at KHCC, Bx* biopsy outside KHCC, Carbo carboplatinum, CTX chemotherapy,
FA fibrillary astrocytoma, GBM glioblastoma, NA not available, OS overall survival, PA pilocytic astrocytoma, RTX radiotherapy, VCRvincristinea This was mentioned only in the referral notes. MRIs were not available for reviewb Owing to the young age of the patient and long history of stable disease (9 months), chemotherapy was administeredc Deteriorated clinically after the sixth session of radiotherapy and treatment was stopped
Table 2 Pathological and immunohistochemical findings
No.. Pathology
DX
Cellularity Pleomo Entrapped
neurons
Mitosis
(hpf)
Apoptosis
(hpf)
VP Necrosis RF EGBs NFP Ki67
(%)
p53
1 PA 1 2 – 0 0 ? – ? – Occasional 1 –
2 PA 2 1 – 0 1 ? – ? – Occasional 8 –
3 PA 1 1 – 0 0 ? – ? – Negative 4 –
4 FA 2 2 ? 0 10 – – – – Occasional 2 –
5 FA 2 1 ? 0 3 – – – – Positive 1 –
6 AA 2 1 ? 0 4 – – – – NA 10 NA
7 AA 2 1 ? 1 0 – – – – Positive 20 NA
8 AA 3 3 ? 1 1 – – – – Positive 20 ?
9 AA 3 3 – 3 4 – – – – NA NA NA
10 AA 3 3 ? 2 8 – – – – NA NA NA
11 AA 3 2 ? 1 3 – – – – Positive NA NA
12 AA 3 3 – 1 2 – – – – Negative 10 –
13 GBM 2 1 – 0 4 ? – – – Negative 30 –
14 GBM 3 2 – 1 10 ? Yes – – NA NA NA
15 GBM 3 3 ? 1 4 ? – – – Positive 40 ?
AA anaplastic astrocytoma, DX diagnosis, EBGs eosinophilic granular bodies, FA fibrillary astrocytoma, grade II, GBM glioblastoma, hpf high-
power field, NFP neurofilament protein, PA pilocytic astrocytoma, Pleomo pleomorphism, RF Rosenthal fibers
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(Figs. 1d, 2d) from two low grade astrocytoma cases,
infiltrative WHO grade II fibrillary astrocytoma and pilo-
cytic astrocytoma, respectively. P53 was negative in both
cases (not shown).
Several variables were tested for possible significant
correlation. The infiltrative versus the circumscribed
growth pattern of tumor correlated significantly with tumor
location (pons vs. outside pons; p = 0.01) and MRI find-
ings (typical vs. atypical; p = 0.03). NFP correlated sig-
nificantly with the presence of entrapped neurons within
the tumor (p = 0.02). Mitosis and the Ki-67 proliferative
index correlated significantly with the tumor grade
(p = 0.01 and p = 0.02, respectively). P53 was the least
useful marker, and although it was positive in two high-
grade glioma cases, it failed to differentiate infiltrative
grade II fibrillary astrocytoma from circumscribed grade I
pilocytic astrocytoma (p = 0.17).
At the time of the study, six patients were alive with
disease, six patients were dead of disease and three patients
were lost to follow-up. The median overall survival for the
whole group was 21.7 months (Fig. 3a). The overall sur-
vival correlated with \6 weeks’ duration of symptoms at
the time of presentation (log rank p = 0.045) (Fig. 3b) and
with a higher grade of tumors as seen on biopsies (log rank
p = 0.023) (Fig. 3c). Other clinical, radiological, patho-
logical and immunohistochemical findings did not correlate
with survival.
Discussion
We report our findings in 15 cases of brain stem glioma
with biopsies that were managed at our center, five of
which were previously reported [8]. The findings are at
Fig. 1 A case of diffuse pontine glioma. a Axial T2W MRI showing
encasement of the basilar artery by a hyperintense lesion (typical
MRI). b Biopsy shows infiltration of pre-existing neurons by low-
grade infiltrative astrocytoma showing no evidence of mitosis,
vascular proliferation or necrosis. The entrapped neurons appear
normal (H&E 940). c Neurofilament protein immunostain highlight-
ing the infiltrative nature of the tumor cells (920). d Ki-67
proliferative index is low (1.2 %) (920)
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large in concordance with international literature apart
from the marked predominance of female patients, a pre-
viously described observation by our group.
Obtaining diagnostic biopsy from BSG continues to be
controversial in the literature [4, 17]. Recently, new tests
have been introduced that might help in confirming the
diagnosis, and predicting the prognosis and response to
potential targeted therapy, thus advocating the need for
obtaining biopsies from pontine glioma [18, 19]. However,
these tests are still expensive, demanding special specimen
collection and storage facilities, and until they become
readily feasible, the reporting (neuro)pathologist has to
deal with small stereotactic biopsies during routine clinical
daily practice, on which depend further management and
disclosure of the prognosis.
Although pilocytic astrocytoma and infiltrative WHO
grade II fibrillary astrocytoma are both low-grade tumors,
they carry different prognoses and natural histories,
necessitating their differentiation [4]. Low-grade fibrillary
astrocytoma might only be one component in an otherwise
heterogeneous infiltrative astrocytoma with additional
high-grade components that were not biopsied. In addition,
progression to high-grade glioma is a well-known phe-
nomenon in grade II fibrillary astrocytoma, but not in pil-
ocytic astrocytoma. While radiotherapy can be offered to
infiltrative tumors, it is usually contraindicated in pilocytic
astrocytomas.
One of the first challenges in segregating pilocytic from
infiltrative astrocytoma is deciding on the growth pattern of
the tumor, i.e., circumscribed versus infiltrative. Although
the presence of entrapped normal-looking neurons should
serve as a clue to the infiltrative nature of the tumor, this
feature can sometimes be misleading. Normal-looking
entrapped neurons can be misinterpreted as an integral
component of the tumor, leading to an erroneous diagnosis
of another WHO grade I circumscribed tumor, i.e.,
Fig. 2 A case of exophytic brain stem glioma. a Sagittal T1W MRI
showing a hyperintense mass at the junction between the mid-brain
and the pons (atypical MRI). b Biopsy shows low cellularity of the
tumor with many Rosenthal fibers and perivascular lymphocytic
infiltration. No evidence of entrapped neurons, mitosis, vascular
proliferation or necrosis (H&E 940). c Neurofilament protein
immunostain highlighting scattered filaments at the edge of the
tumor only (920). d Ki-67 proliferative index is low (\1 %) (920)
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ganglioglioma. Paying attention to the microscopic details
of the neurons should be helpful in this respect [20]. In
ganglioglioma the neurons are dysplastic with bi- and mul-
tinucleated forms, show abnormal membranous aggregation
of Nissel substance and on low-power display abnormal
aggregation, features that all are lacking when innocent
by-standing pre-existing neurons are overrun by the infil-
trative astrocytoma. The infiltrative nature of tumors can be
further supported by the diffuse positive NFP staining
highlighting the pre-existing neuronal fibers. Occasional
NFP-positive fibers can still be seen in biopsies from cir-
cumscribed tumors. However, they are few in number and
widely scattered within the biopsy.
Assigning a grade to the tumor is essential once the
growth pattern and thus tumor group has been determined
[10]. The presence of a single mitotic figure in small
biopsies of infiltrative astrocytoma is sufficient to support
the diagnosis of WHO grade III anaplastic astrocytoma.
Elevated Ki-67 proliferative indices can be used to assist in
guiding the grade of infiltrative astrocytoma, especially
when mitosis or other high-grade features are not detected
in the submitted biopsy [21]. Additionally, the presence of
tumor-cell apoptosis was supportive of infiltrative astro-
cytoma, where their number increased in higher grade
tumors. Tumor cell apoptosis, however, did not correlate
with staining with P53, which was positive in only two
high-grade glioma cases [16]. This is similar to the p53
immunostain frequency reported by Zarghooni et al. [22],
in which a single case only stained for P53. In addition,
P53 was negative in all low-grade tumors and could not
discriminate between low-grade infiltrative and pilocytic
astrocytoma cases in this series. Recently, IDH1 immu-
nostains were negative in cases of BSG as well [23].
Treating DPG has always remained a challenge with
poor overall survival in most studies. Radiotherapy remains
the standard of care [24, 25], offered in the setting of
palliative care. Disclosure of the poor outcome to parents is
encouraged and is well accepted by parents [8]. Chemo-
therapy has not provided relief, and the use of new agents
including temozolomide (TZM) has not been reported to
Fig. 3 a Overall survival for the group of patients. b Survival by duration of symptoms (weeks). c Survival by grade of tumor
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add any survival benefit [26]. Searching for potential
unique targets for treatment is currently under consider-
ation by several research groups. Monje et al. [27]
described a subset of Nestin?, vimentin?, Olig2? neural
precursor-like cells in the developing human ventral pons
that is responsive to the hedgehog signaling pathway, thus
representing a potential therapeutic target. Zarghooni et al.
[22] reported gains in PDFGRA (4 tumors) and PDGFA (2
tumors) representing 50 % of the tumor samples examined,
suggesting that PDGFR inhibitors may potentially be used
as therapeutic agents. Similar results were obtained by
Puget et al. [28] in which oligodendroglial-differentiating,
PDGFRA-driven tumors had worse outcomes than those of
other tested groups of patients, supporting the potential role
of PDGFRA in the tumorigenesis of DPG. Additionally,
PARP-1 overexpression was reported in few patients,
offering a possible explanation for temozolomide and
radiotherapy resistance in DPG [22]. Other identified
genetic abnormalities include epidermal growth factor
variant III (EGFRvIII) [29] and PI3KCA [30], all acting as
a potential source for future targeted therapy.
In conclusion, this study summarizes the experience of a
cancer center on a limited number of cases of BSG that
were biopsied. Duration of symptoms prior to presentation
of \6 weeks and grade of tumor as evaluated on biopsies
were the only parameters with a significant relation to
survival. Paying attention to a few details on the H&E
slides can help in clarifying two important parameters of a
tumor: the circumscribed versus infiltrative growth pattern
and the grade of an infiltrative tumor, both of which have
important implications for management, survival and
prognosis. A limited panel of immunohistochemistry can
be used as an adjunct in equivocal cases. Obtaining biop-
sies from brainstem gliomas should be encouraged to
enhance understanding of the pathogenesis and potentially
to guide treatment through targeted therapy.
Acknowledgments The authors would like to thank Dr. Luna Zaru
and Ms. Dalia Remawi for their help in the statistical analysis and
interpretation.
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