ArticlePDF Available

Abstract and Figures

Angiocentric glioma is a recently recognized benign brain tumor with unknown histogenesis. Most of these tumors are mitotically low in activity in accord with their benign clinical course. However, increased mitotic activity has been noted in several cases, one of which had an ultimately fatal outcome. Here, the authors present a tumor showing angiocentric glioma and glioblastoma-like features, with recurrence of the lower-grade component after radiotherapy. A 15-year-old boy presented with a 3-month history of progressive left-sided weakness and headache. Magnetic resonance imaging showed a large heterogeneous mass in the right frontal lobe, with mild post-Gd enhancement. A gross-total resection was obtained. Histopathological examination of the resected tissue revealed a tumor with 2 distinct appearances: 1) a mildly to moderately cellular infiltrating tumor with angiocentric glioma characteristics, and 2) a markedly cellular glioblastoma-like tissue with necrosis and microvascular proliferation. The patient received a course of postoperative radiotherapy to 59.4 Gy in 33 fractions administered over the course of 6.5 weeks, but his tumor recurred 4 months after resection. A second resection was then performed. The recurrent tumor exhibited radiation-induced changes and persistent characteristics of angiocentric glioma, but it had fewer malignant features; the mitotic activity was lower, and there was no necrosis or microvascular proliferation. The findings in this case, along with those in several previously reported cases, suggest that angiocentric gliomas may have a malignant variant or malignant transformation. Angiocentric gliomas with malignant features tend to recur, for which surgical intervention followed by radiotherapy and chemotherapy should be offered as a therapeutic option.
Content may be subject to copyright.
J Neurosurg Pediatrics 11:350–355, 2013
350
J Neurosurg: Pediatrics / Volume 11 / March 2013
©AANS, 2013
A
ngiocentric glioma has been recently recognized
as a distinct clinicopathological entity in the re-
vised 2007 WHO Classication of Tumours of
the Central Nervous System.
2
It has been described as an
epileptogenic benign (WHO Grade I) brain tumor that
may be cured by excision alone. Its histogenesis remains
unknown, but there are clearly features of ependymal
differentiation.
6,17
Several dozen angiocentric gliomas
have been reported to date,
6–8,12,14,15,17
but in only a few
cases have mitoses been noted.
6,15,17
Several angiocentric
gliomas, including those with mitoses, have been treated
with radiotherapy, but the effects of radiotherapy have
not been evaluated histologically.
6–8,15,17
Here, we present
a unique tumor containing both angiocentric glioma and
glioblastoma-like features, in which the anaplastic com-
ponent was largely absent in the recurrent, posttreatment
lesion.
Case Report
Presentation and Examination. This 15-year-old boy
presented with a 3-month history of progressive left-sided
Malignant glioma with angiocentric features
Case report
Jian-Qiang Lu, M.D., Ph.D.,
1
SaMir PateL, M.D.,
2
BeverLy a. WiLSon, M.D.,
3
Jeffrey Pugh, M.D.,
4
anD vivek Mehta, M.D.
4
Departments of
1
Laboratory Medicine and Pathology,
2
Oncology,
3
Pediatrics, and
4
Surgery, University of
Alberta, Edmonton, Alberta, Canada
Angiocentric glioma is a recently recognized benign brain tumor with unknown histogenesis. Most of these
tumors are mitotically low in activity in accord with their benign clinical course. However, increased mitotic activ-
ity has been noted in several cases, one of which had an ultimately fatal outcome. Here, the authors present a tumor
showing angiocentric glioma and glioblastoma-like features, with recurrence of the lower-grade component after
radiotherapy. A 15-year-old boy presented with a 3-month history of progressive left-sided weakness and head-
ache. Magnetic resonance imaging showed a large heterogeneous mass in the right frontal lobe, with mild post-Gd
enhancement. A gross-total resection was obtained. Histopathological examination of the resected tissue revealed
a tumor with 2 distinct appearances: 1) a mildly to moderately cellular inltrating tumor with angiocentric glioma
characteristics, and 2) a markedly cellular glioblastoma-like tissue with necrosis and microvascular proliferation. The
patient received a course of postoperative radiotherapy to 59.4 Gy in 33 fractions administered over the course of 6.5
weeks, but his tumor recurred 4 months after resection. A second resection was then performed. The recurrent tumor
exhibited radiation-induced changes and persistent characteristics of angiocentric glioma, but it had fewer malignant
features; the mitotic activity was lower, and there was no necrosis or microvascular proliferation. The ndings in this
case, along with those in several previously reported cases, suggest that angiocentric gliomas may have a malignant
variant or malignant transformation. Angiocentric gliomas with malignant features tend to recur, for which surgical
intervention followed by radiotherapy and chemotherapy should be offered as a therapeutic option.
(http://thejns.org/doi/abs/10.3171/2012.11.PEDS12234)
key WorDS •  angiocentric glioma  •  malignant transformation  • 
pathology  •  radiotherapy  •  anaplastic ependymoma  •  glioblastoma  • 
oncology
Abbreviations used in this paper: EMA = epithelial membrane
antigen; GTR = gross-total resection.
J Neurosurg: Pediatrics / Volume 11 / March 2013
Malignant glioma with angiocentric features
351
weakness starting with his left hand. He also complained
of headache, vomiting, and decreased visual acuity. Phys-
ical examination at admission revealed left hemiparesis.
Craniospinal MRI showed a large (5.3 × 6.0 × 6.9 cm)
mass in the right frontal lobe. The mass was heteroge-
neously hypointense on T1-weighted images and hetero-
geneously hyperintense on T2-weighted images (Fig. 1A),
and it mildly enhanced after Gd administration (Fig. 1B),
which was associated with a 1.2-cm right-to-left midline
shift and T2 hyperintense signal abnormality in the ad-
jacent white matter. On diffusion-weighted imaging, the
apparent diffusion coefcient of the mass was approxi-
mately 9.9 × 10
-4
mm
2
/sec and predominantly similar to
that of the brain tissue (Fig. 1C). The mass on MR spec-
troscopy demonstrated a high choline content.
Initial Resection. The patient underwent an emer-
gency right frontal craniotomy. After the dura mater was
incised, the mass was easily identied. Circumferential
dissection of the planes was performed, and the mass was
internally debulked and removed using the Cavitron ultra-
sonic aspirator. An intraoperative frozen section obtained
from the periphery of that mass showed morphological
features consistent with a glioma. A GTR was achieved.
Histopathological Examination. On gross examina-
tion, the 7.0 × 6.0 × 2.6cm surgically excised tissue was
soft, rubbery, and heterogeneous. Histopathological ex-
amination revealed a tumor with varying hypercellularity
(Fig. 2). Most areas had mild to moderate hypercellularity
with predominantly spindle-shaped cells and angiocen-
tric growth pattern (Fig. 2A–F), in which many tumor
cells were radially and longitudinally aligned along the
cerebral blood vessels (Fig. 2A). The subpial aggrega-
tion of neoplastic cells was also present (Fig. 2B, arrows).
Inltrating growth of this tumor into the adjacent brain
parenchyma was obvious, with occasional entrapped
neurons (Fig. 2C, arrow). Neurolament protein–immu-
noreactive axons were abundant in the tumor except for
in the perivascular areas (Fig. 2D). This tumor was dif-
fusely immunoreactive for GFAP (Fig. 2E) and vimentin.
Epithelial membrane antigen immunostaining exhibited
dotlike and ringlike positivity (Fig. 2F), suggestive of
ependymal differentiation. In contrast, other areas of the
tumor were markedly hypercellular, with scattered mito-
ses, microvascular proliferation (Fig. 2G), and necrosis
(Fig. 2H). The MIB-1 labeling index of proliferation was
moderately high (Fig. 2I), and IDH1 (R132H) immunos-
taining was negative.
9
Focal immunoreactivity for epider-
mal growth factor receptor was seen in this tumor (not
shown).
5
Postoperative Radiotherapy. The resection resulted
in improvement of the patient’s facial asymmetry and
strength on the left side (Fig. 3A). Postoperatively, it was
noted that he had persistent visual loss. Ophthalmologi-
cal examination revealed severe bilateral central visual
loss. Moderate bilateral papilledema was found, which
was suspected to exist prior to the resection. Cranial ra-
diation (59.4 Gy in 33 fractions) was administered over
a course of 6.5 weeks. During radiotherapy, the patient
had continuous improvement in his left hemiparesis, but
visual loss persisted. His family had noted a few episodes
of possible seizures. An electroencephalographic study
revealed moderate abnormalities and recorded 2 subclini-
cal electrographic seizures, for which he started receiving
Tegretol.
Tumor Recurrence. A follow-up MRI study per-
formed 5 weeks after radiation therapy (16 weeks after
the resection) showed thickened enhancement after Gd
administration in the medial aspect of the surgical mar-
gins (Fig. 3B), compared with the preradiation MRI study
(Fig. 3A), which was highly suspicious for the tumor re-
currence. Repeat MRI performed 11 weeks later revealed
increased nodular tissue and more thickened enhance-
ment post-Gd preferentially along the resection cavity
(Fig. 3C). The patient had increased left-sided weakness.
Second Resection. After opening the dura, the tumor
was relatively distinct from the brain tissue. Tumor lob-
ules were dissected without difculty, and superior fron-
tal quadrant resection (GTR) was achieved.
Histopathological Examination. The resected tis-
sue, examined totally, measured 4.2 × 2.0 × 1.5 cm in
aggregate. Its histopathological features were somewhat
similar to those of the primary resected tumor described
earlier. Spindle-shaped cells (Fig. 4A) and an angiocen-
tric growth pattern (Fig. 4A–C) persisted in most areas.
Radiation-induced changes, including cytological atypia
particularly with increased eosinophilic cytoplasm (Fig.
4B) and tissue rarefaction (Fig. 4C), were focally prom-
Fig. 1. Preoperative T2-weighted (A), Gd-enhanced T1-weighted (B), and diffusion-weighted (C) MR images revealing a het-
erogeneous tumor in the right frontal lobe.
J. Q. Lu et al.
352
J Neurosurg: Pediatrics / Volume 11 / March 2013
inent.
3
Tumor cells were strongly immunoreactive for
GFAP. Dotlike and ringlike EMA immunoreactivity was
again present, which was consistent with the electron mi-
croscopy nding of microvilli in the cytoplasm of cells
(Fig. 4D). Mitoses were rarely identied, and the MIB-1
labeling index was much lower than that of the primary
tumor (Fig. 4E). Neither necrosis nor microvascular pro-
liferation was found. This tumor was negative for p53, but
it was largely immunoreactive for p16 (Fig. 4F).
Postoperative Course. After the second resection, the
patient developed increasing fatigue and left foot drop.
Four weeks later, he was started on chemotherapy with
oral temozolomide (400 mg daily for 5 days every month),
which was scheduled for 10 cycles or months. The MRI
studies performed at the 9-, 14-, and 30-week follow-up
visits after the second resection revealed no tumor recur-
rence other than the postsurgical changes and no evidence
of a metastatic lesion (Fig. 3D).
Discussion
To our knowledge this is the rst report of a glioblasto-
ma-like tumor containing the characteristic features of an
angiocentric glioma. Angiocentric gliomas with increased
mitotic activity have been previously reported in 3 case
studies. Table 1 summarizes the clinical, radiological, and
pathological features, as well as the outcomes of those cas-
es, in comparison with the present case. The present case,
along with these 3 angiocentric glioma cases with anaplas-
tic features, suggests that angiocentric glioma may have a
malignant variant or malignant transformation.
The cell origin of angiocentric glioma is unknown,
but the presence of ependymal features has been noted by
all authors.
2,6–8,12,14,15,17
One suggestion is that angiocentric
gliomas are variants of cortical ependymomas.
16
Ependy-
mal differentiation is expressed as an ultrastructural nd-
ing of the ependymal characteristics and immunohisto-
chemical dotlike immunoreactivity for EMA.
2,6–8,12,14,15,17
The diffusely inltrating quality, often with prominent
subpial accumulation, is, in contrast, not usually a feature
of ependymomas. Our present case was otherwise consis-
tent with a glioblastoma, except that angiocentric glioma
and ependymal characteristics were also identied. Inter-
estingly, our present case demonstrated 2 additional fea-
tures: a modest value of the apparent diffusion coefcient
on diffusion-weighted imaging in favor of ependymal dif-
ferentiation,
1,13
and the immunoreactivity for p16 tumor
suppressor gene protein, which is more often seen with
malignant astrocytomas than ependymal tumors.
4,10,11
The
absence of mutant IDH1 (R132H) protein expression, as
reported in angiocentric gliomas, helps further distin-
Fig. 2. Photomicrographs of a tumor demonstrating the morphology of spindle-shaped cells preferentially aligned along the
cerebral blood vessels (A), the subpial aggregation (B, arrows), and infiltrating growth with occasional entrapped neurons (C, ar-
row) and abundant neurofilament protein–immunoreactive axons except the perivascular areas (D), immunoreactivity for GFAP
(E), dotlike and ringlike immunoreactivity for EMA (F, arrow indicates ringlike positivity). The tumor shows focally malignant
features with increased cellularity, microvascular proliferation (G), necrosis (H), and a high MIB-1 labeling index of proliferation
(I). Original magnification ×200 (A, B, and G), ×400 (C, E, F, and I), and ×100 (D and H).
J Neurosurg: Pediatrics / Volume 11 / March 2013
Malignant glioma with angiocentric features
353
guish the present tumor from inltrative astrocytomas
(except for primary glioblastomas).
9
Although angiocentric glioma has been regarded as an
epileptogenic tumor, several previously reported patients
with angiocentric gliomas did not initially present with sei-
zures but with other symptoms, especially headache.
7,12,17
In the present case, the presenting symptoms were left-
sided weakness and headache, which may correspond to
the patients rapidly growing tumor with glioblastoma-like
features. Although chronic atrophic papilledema may have
contributed to the visual eld loss, the cause of persistent
visual loss in the present case is unknown. With regard to
the prognosis, 2 previously reported angiocentric gliomas
with anaplastic features recurred 12 and 21 months after
their primary resection.
6,17
The tumor in the present patient
recurred 4 months after the primary resection and a second
resection was performed. No recurrence was observed 7
months after the second resection.
The histopathological features of the second resected
tumor (lower mitotic activity and absence of necrosis and
microvascular proliferation) were much less malignant
than those of the primary resected tumor. These histo-
pathological changes in the second resection may reect
the benecial effects of the radiotherapy following the
primary resection. No recurrence in the next 7 months
after the second resection may also be accredited to the
addition of high-dose temozolomide.
Conclusions
Angiocentric gliomas may undergo malignant trans-
formation or include a malignant variant. The biological
behavior of such lesions is unclear given the paucity of
cases. Angiocentric gliomas with malignant features tend
to recur, and their prognosis might be equivalent to that
of glioblastoma or anaplastic ependymoma. These angio-
Fig. 3. Gadolinium-enhanced T1-weighted MR images obtained 3
weeks after the primary resection (A, preradiotherapy), 16 weeks after
the primary resection (B, 5 weeks postradiotherapy, highly suspicious
for tumor recurrence), and 27 weeks after the primary resection (C, 16
weeks postradiotherapy, conrming the tumor recurrence leading to its
second resection). A further follow-up image obtained 30 weeks after
the second resection (D, 58 weeks after the primary resection) shows
no tumor recurrence.
Fig. 4. Photomicrographs of the recurrent tumor showing the retained morphology of the angiocentric growth of tumor cells
(AC) and spindle-shaped cells (A), as well as radiation-induced changes including cytological atypia (B) and tissue rarefaction
(C). D: Electron microscopy image demonstrating microvilli (arrow) in the cytoplasm of cells around the blood vessel. v = vas-
cular lumen. E and F: The recurrent tumor exhibits lower MIB-1 labeling index of proliferation (E) but is largely immunoreactive
for the p16 tumor suppressor gene protein (F). Original magnification ×200 (A and B), ×100 (C), ×33,600 (D), and ×400 (E and F).
J. Q. Lu et al.
354
J Neurosurg: Pediatrics / Volume 11 / March 2013
centric gliomas with malignant features should be treated
with radiotherapy and chemotherapy following GTR.
Disclosure
The authors report no conflict of interest concerning the mate-
rials or methods used in this study or the findings specified in this
paper.
Author contributions to the study and manuscript preparation
include the following. Conception and design: all authors. Acqui-
sition of data: all authors. Analysis and interpretation of data: all
authors. Drafting the article: Lu, Patel, Wilson, Mehta. Critically
revising the article: all authors. Reviewed submitted version of man-
uscript: all authors. Approved the final version of the manuscript on
behalf of all authors: Lu. Administrative/technical/material support:
all authors. Study supervision: Lu, Mehta.
Acknowledgments
The authors thank Peter C. Burger, M.D., of the Department
of Pathology at Johns Hopkins University, Baltimore, Maryland, for
his help with the pathology diagnosis in this case and critical review
of the manuscript, and Cynthia Hawkins, M.D., at The Hospital for
Sick Children, Toronto, Ontario, Canada, for her help with preform-
ing IDH1 and EGFR immunohistochemical studies.
References
1. Bull JG, Saunders DE, Clark CA: Discrimination of paediat-
ric brain tumours using apparent diffusion coefcient histo-
grams. Eur Radiol 22:447457, 2012
2. Burger PC, Jouvet A, Preusser M, Hans VH, Rosenblum MK,
Lellouch-Tubiana A: Angiocentric glioma, in Louis DN, Oh-
gaki H, Weistler OD, et al (eds): WHO Classication of Tu-
mours  of the Central Nervous System,  ed 4. Lyon: IARC
Press, 2007, pp 9293
3. Ellison DW, Perry A, Rosenblum M, Asa S, Reid R, Louis
DN: Tumors: non-neuroepithelial tumors and secondary ef-
fects, in Love S, Louis DN, Ellison DW (eds): Greeneld’s 
Neuropathology,  ed  8. London: Hodder Arnold Publishers,
2008, pp 2140–2143
4. Jen J, Harper JW, Bigner SH, Bigner DD, Papadopoulos N,
Markowitz S, et al: Deletion of p16 and p15 genes in brain
tumors. Cancer Res 54:63536358, 1994
5. Kogiku M, Ohsawa I, Matsumoto K, Sugisaki Y, Takahashi H,
Teramoto A, et al: Prognosis of glioma patients by combined
immunostaining for survivin, Ki-67 and epidermal growth
factor receptor. J Clin Neurosci 15:1198–1203, 2008
6. Miyahara H, Toyoshima Y, Natsumeda M, Uzuka T, Aoki H,
Nakayama Y, et al: Anaplastic astrocytoma with angiocentric
ependymal differentiation. Neuropathology 31:292–298, 2011
7. Mott RT, Ellis TL, Geisinger KR: Angiocentric glioma: a case
report and review of the literature. Diagn  Cytopathol 38:
452456, 2010
8. Preusser M, Hoischen A, Novak K, Czech T, Prayer D, Hainfell-
ner JA, et al: Angiocentric glioma: report of clinico-pathologic
and genetic ndings in 8 cases. Am J  Surg Pathol 31:1709
1718, 2007
9. Raghunathan A, Olar A, Vogel H, Parker JR, Coventry SC,
Debski R, et al: Isocitrate dehydrogenase 1 R132H mutation
is not detected in angiocentric glioma. Ann Diagn Pathol 16:
255–259, 2012
10. Rajaram V, Leuthardt EC, Singh PK, Ojemann JG, Brat DJ,
Prayson RA, et al: 9p21 and 13q14 dosages in ependymomas.
A clinicopathologic study of 101 cases. Mod Pathol 17:9–14,
2004
11. Rao LS, Miller DC, Newcomb EW: Correlative immunohisto-
chemistry and molecular genetic study of the inactivation of
TABLE 1: Reported cases with the features of angiocentric glioma and malignancy*
Authors &
Year
Age at Op
(yrs), Sex Clinical Presentation Location on Preop MRI Pathology Treatment Outcome
Wang et al.,
2005
26, M 2-yr Hx seizures lt frontal lobe, initially noncontrast-
enhancing lesion
features of AG & initially low-grade
astrocytoma; recurrence w/ mi-
toses, diagnosed as anaplastic
astrocytoma
initial PR; for recurrence, PR fol-
lowed by 60 Gy RT over 6 wks in
30 fractions, & chemo (procarba-
zine, carmustine, & vincristine)
recurrence (w/ seizures) at 21
mos; died of disease 62 mos
after initial op
Sugita et
al., 2008
6, M 5-mo Hx seizures rt occipitoparietal cortex, ill-dened
high-signal lesion on FLAIR & T2-
weighted MRI
features of AG & mitoses (1/50
hpf; MIB-1 labeling index 8%)
resection of lesion & surrounding
epileptogenic cortex
no recurrence at 9-mo follow-up
Miyahara et
al., 2011
66, F 6-yr Hx intermittent
headaches, new-
onset seizures
rt insular gyri/anterior temporal lobe,
large hyperintense lesion on FLAIR
& T2-weighted MRI w/ postcontrast
enhancement in insular region
2 different morphologies: features
of AG; astrocytoma w/ mitoses
& MIB-1 labeling index >5%
PR followed by RT & chemo (temo-
zolomide)
recurrence (w/ irregularly en-
hanced lesion) after ~1 yr &
growing gradually in deep
white matter
present
case
15, M 3-mo Hx headaches &
lt-sided weakness
rt frontal lobe large (5.3 × 6.0 × 6.9
cm) heterogeneously hyperintense
lesion on T2-weighted MRI w/ mild
postcontrast enhancement
2 distinct appearances: features
of AG; malignant astrocytoma w/
mitoses, necrosis, & microvascu-
lar proliferation
initial GTR, followed by 59.4 Gy RT
over 6.5 wks in 33 fractions; for
recurrence, GTR followed by
chemo (high-dose temozolomide)
recurrence 16 wks after initial
op; after 2nd op, no more re-
currence at 30-wk follow-up
* AG = angiocentric glioma; chemo = chemotherapy; Hx = history of; PR = partial resection; RT = radiotherapy.
J Neurosurg: Pediatrics / Volume 11 / March 2013
Malignant glioma with angiocentric features
355
the p16INK4A genes in astrocytomas. Diagn Mol Pathol 6:
115122, 1997
12. Rho GJ, Kim H, Kim HI, Ju MJ: A case of angiocentric glio-
ma with unusual clinical and radiological features. J Korean 
Neurosurg Soc 49:367–369, 2011
13. Rumboldt Z, Camacho DL, Lake D, Welsh CT, Castillo M:
Apparent diffusion coefcients for differentiation of cerebel-
lar tumors in children. AJNR Am J Neuroradiol 27:1362
1369, 2006
14. Shakur SF, McGirt MJ, Johnson MW, Burger PC, Ahn E, Car-
son BS, et al: Angiocentric glioma: a case series. Clinical ar-
ticle. J Neurosurg Pediatr 3:197202, 2009
15. Sugita Y, Ono T, Ohshima K, Niino D, Ito M, Toda K, et al:
Brain surface spindle cell glioma in a patient with medically
intractable partial epilepsy: a variant of monomorphous an-
giocentric glioma? Neuropathology 28:516–520, 2008
16. Van Gompel JJ, Koeller KK, Meyer FB, Marsh WR, Burger
PC, Roncaroli F, et al: Cortical ependymoma: an unusual
epileptogenic lesion. Clinical article. J Neurosurg 114:1187
1194, 2011
17. Wang M, Tihan T, Rojiani AM, Bodhireddy SR, Prayson RA,
Iacuone JJ, et al: Monomorphous angiocentric glioma: a dis-
tinctive epileptogenic neoplasm with features of inltrating
astrocytoma and ependymoma. J Neuropathol  Exp Neurol
64:875881, 2005
Manuscript submitted April 29, 2012.
Accepted November 12, 2012.
Please include this information when citing this paper: published
online December 14, 2012; DOI: 10.3171/2012.11.PEDS12234.
Address correspondence to: Jian-Qiang Lu, M.D., Ph.D., Neuro-
pathology Section, 5B2.24 WCM Health Sciences Centre, Univer-
sity of Alberta, 8440-112 Street, Edmonton, Alberta, Canada T6G
2B7. email: jian-qiang.lu@ualberta.ca.
... There are seven tumour recurrences from approximately 100 tumours with angiocentric pattern described in the literature [2][3][4][5][6][7][8][9][10][11][12]. Most of them had atypical histopathological findings like pleomorphism, mitotic activity, or high Ki-67 index and angiocentric pattern with ependymal differentiation. ...
... Most of them had atypical histopathological findings like pleomorphism, mitotic activity, or high Ki-67 index and angiocentric pattern with ependymal differentiation. Three cases progressed to high-grade glioma without AG features [4,7,8,11]. Two cases of high-grade gliomas with angiocentric features have been described [7,8]. ...
... Three cases progressed to high-grade glioma without AG features [4,7,8,11]. Two cases of high-grade gliomas with angiocentric features have been described [7,8]. These few cases, including ours, raise the question of whether high-grade astrocytomas can mimic angiocentric glioma or if the progression of early undetected angiocentric glioma exists. ...
Article
Full-text available
Angiocentric features are uncommon in high-grade World Health Organisation (WHO) brain tumours, whilst they are typical for WHO grade I tumours, e.g. angiocentric gliomas. We present an unusual glial tumour that occurred in a 59-year-old man. The tumour had equivocal radiologic and histopathologic features, especially a characteristic angiocentric pattern, low-to-moderate Ki67, and dot-like epithelial membrane antigen expression. The tumour did not show features characteristic for glioblastoma; however, it recurred as glioblastoma four months later. Based on this case, we show that high-grade WHO brain tumours may show an angiocentric pattern typical for low-grade WHO brain tumours, such as angiocentric gliomas.
... Vast majority of the cases presented a benign course of the disease -some patients with a history of the seizures counted in decades [20,23]. Despite that, supposedly malignant variants of AG (possibly WHO III), characterized by a higher mitotic index, vascular proliferation and necroses were also observed [1,15]. The elective method of treatment is gross total resection, but subtotal resection and chemotherapy and radiotherapy had also been used, especially in more difficult locations or to handle rare, high grade variants [1,5,16,20]. ...
Article
Full-text available
Angiocentric glioma (AG) is a newly-classified, very rare, WHO grade I central nervous system (CNS) lesion, occurring usually in children and young adults. Only 52 patients with AG have been reported so far, making it one of the rarest neuropathological entities. Hereby we present two new cases of AG in young subjects with detailed neuropathological investigations and a neuroradiological picture along with a brief summary of all already published literature reports of this tumor. Histopathological examination of the resected tissue from both cases revealed similar changes characteristic of AG. The tumors were composed of spindle-like, elongated cells, forming characteristic pseudorosettes around vessels and diffusively infiltrating surrounding tissue, trapping neurons between tumor cells. Noticeably, some neoplastic cells encrusting vessels extended far beyond the main tumor mass. Hypothetically, this may be responsible for the recurrence of the tumor even in the case of apparently total excision. In immunohistochemistry, AG cells were glial fibrillary acidic protein (GFAP) and vimentin positive, also exhibiting a strikingly significant epithelial membrane antigen (EMA) dot-like staining pattern. In one of the cases, electron microscopy revealed ependymal differentiation features such as microvilli and cilia. Taken together, all these data strongly confirm a dual astroglial-ependymal nature of the tumor. Follow up corroborates benign character of this neoplasm. Both AGs reported here were immunonegative for the product of the mutated IDH-1 gene what, according to our best knowledge, has never been reported so far. It may suggest that in their pathogenesis AGs differ from grade II astrocytomas, which in most cases harbor a mutation of IDH-1. Noteworthy, neuroimaging in our cases was relatively characteristic but not conclusive, therefore biopsy (at least) is mandatory. A newly proposed so called "A-B-C" classification of long-term epilepsy-associated tumors (LEATs) places AG in a category named ANET. The authors shortly review the A-B-C classification of LEATs.
... Vast majority of the cases presented a benign course of the disease -some patients with a history of the seizures counted in decades [20,23]. Despite that, supposedly malignant variants of AG (possibly WHO III), characterized by a higher mitotic index, vascular proliferation and necroses were also observed [1,15]. The elective method of treatment is gross total resection, but subtotal resection and chemotherapy and radiotherapy had also been used, especially in more difficult locations or to handle rare, high grade variants [1,5,16,20]. ...
Article
Full-text available
Background and purpose: Angiocentric gliomas (AGs) are epileptogenic low-grade gliomas in young patients. We aimed to investigate the MRI findings of AGs and systematically review previous publications and three new cases. Methods: We searched PubMed, Elsevier's abstract and citation database, and Embase databases and included 50 patients with pathologically proven AGs with analyzable preoperative MRI including 3 patients from our institution and 47 patients from 38 publications (median age, 13 years [range, 2-83 years]; 35 men). Two board-certified radiologists reviewed all images. The relationships between seizure/epilepsy history and MRI findings were statistically analyzed. Moreover, clinical and imaging differences were evaluated between supratentorial and brainstem AGs. Results: Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain parenchymal atrophy were observed in 23 out of 50 (46.0%), 10 out of 50 (20.0%), and 14 out of 50 (28.0%) patients, respectively. Intratumoral T1-weighted high-intensity areas were observed significantly more frequently in patients with stalk-like signs (positive, 9/10 vs. negative, 14/40, p = .0031) and regional atrophy (13/14 vs. 10/36, p = .0001). There were significant relationships between the length of seizure/epilepsy history and presence of intratumoral T1-weighted high-intensity area (median 3 years vs. 0.5 years, p = .0021), stalk-like sign (13.5 vs. 1 year, p < .0001), and regional atrophy (14 vs. 0.5 years, p < .0001). Patients with brainstem AGs (n = 7) did not have a seizure/epilepsy history and were significantly younger than those with supratentorial AGs (median, 5 vs. 13 years, p < .0001, respectively). Conclusions: Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain atrophy were frequent imaging features in AG. We also found that affected age was different between supratentorial and brainstem AGs.
Article
Background Angiocentric glioma (AG) is a rare, low-grade glioma with slow growth. In 2007, AG was first classified as a solid tumor according to the WHO classification of the central nervous system (WHO class I). The outcome and prognosis of most of the cases are very good, but a few cases with tumor metastasis and disease progression, even death, have been reported. We report a case and systematically analyze previous literature to increase our understanding of the disease and determine the factors that may affect disease progression to make prognostic judgments. Case presentation A young male patient complained of a 3-year history of epilepsy. Anti-epileptic drug treatment was ineffective. An imaging examination revealed a lesion in the left parietal cortex area. Thus, the lesion was completely resected. The pathological diagnosis was angiocentric glioma. During a follow-up of two years, the patient had epilepsy relief controlled by sodium valproate and a disease-free period. Conclusion AG is an epilepsy-related low-grade glioma that heals after complete resection in most reported cases. However, few reported cases have had disease progression and death. This result may be due to the pathological complexity of the diseased tissue. In addition, AG is usually found to have an MYB–QKI rearrangement on genetic analysis. Due to the small number of reported cases and studies, our understanding and knowledge of this disease are still lacking. The potential malignant changes and prognostic factors need to be verified in more than clinical cases and basic research in the future.
Article
Full-text available
Purpose The prevalence of gallstones in children has increased over the last years. Choledocholithiasis (CD) is present in up to 30% of the cases. There is a scarcity of studies on the management of choledocholithiasis in children. The aim of this study was to develop a score that would allow predicting accurately the risk of CD in children with gallstones and reduce the number of non-therapeutic ERCP. Materials and methods We conducted a retrospective study in children with gallstones and suspected CD seen between January 2010 and December 2019. The main outcome was the presence of CD confirmed by at least one of the following diagnostic tests: magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and/or intraoperative cholangiography (IOC). We developed a risk score based on the presence or absence of the following risk factors: acute biliary pancreatitis, ascending cholangitis, elevated liver function tests (AST, ALT, total bilirubin [TB, ≥ 2 mg/dl], conjugated bilirubin, gamma-glutamyl transpeptidase, and alkaline phosphatase), CD on ultrasound (US; this was considered predictive but not confirmatory of CD), and dilation of the common bile duct (> 6 mm) by US. The score was divided into three different categories: low risk (no risk factors), intermediate risk (one risk factor present), high risk (≥ 2 risk factors present or ascending cholangitis). Given the main goal of reducing the number of diagnostic ERCPs, a very-high-risk subgroup (3 risk factors present or ascending cholangitis) was identified. Results We reviewed 133 patients with gallstones and suspected CD. In 56 (42.1%) patients, the presence of CD was confirmed by one or more of the definitive diagnostic tests (MRCP, ERCP, and IOC). The following variables were found to be the strongest predictors of CD: ascending cholangitis, TB ≥ 2 mg/dl, common bile duct > 6 mm, and the presence of CD by US. The positive predictive value for CD was 7.5% in the low-risk group (OR 0.06, P = < 0.001); 22.9% in the intermediate-risk group (OR 0.31, P = 0.007); 77.6% in the high-risk group (OR 20.14, P = < 0.001); and 95.7% in very-high-risk subgroup (OR 49.18, P = < 0.001). Conclusion The risk score proposed in this study predicts accurately the presence of CD in children with gallstones. It can serve as a helpful tool to triage the need for costly and complex studies in the workup of CD, particularly in centers with limited resources. Finally, due to its high specificity and positive predictive value (PPV), the use of the very-high-risk criteria would allow for an important decrease in the number of non-therapeutic ERCP.
Article
Background: Angiocentric glioma (AG) is an epileptogenic low grade (World Health Organization grade I) glial tumor with astrocytic and ependymal differentiation, most commonly affecting the pediatric and adolescent population. Despite its infiltrating histological growth kinetics, it is widely accepted that AG has a low potential for aggressive behavior. Case description: We present the case of a 42-year-old man who represents the first documented case of not only extracranial manifestation of AG, but also spinal metastatic dissemination. Our patient initially presented with a generalized tonic clonic seizure; following a biopsy, he was diagnosed with a low-grade supratentorial astrocytoma and subsequently received fractionated radiotherapy. He presented 10 months later with worsening dorsal column symptoms and was found to have a contrast-enhancing intradural extramedullary lesion that was surgically resected and histologically confirmed as an AG. Conclusion: Further research is required to examine the microenvironment and potential for malignant change in this tumor.
Article
Angiocentric glioma (AG) is a low grade glioma, that was first described in 2002. Since this description, 83 patients with AG have been described, including ours. AG typically presents in childhood with medically refractory seizures that are cured with gross surgical resection. Whilst the natural history is that of a benign tumour, there have been reports of recurrence, transformation, and malignant features that suggest that AG is potentially malignant. We add to the literature a case of a 16-year-old girl who presented in May 2011 with a 3-month history of complex partial seizures, with MRI showing a T2-weighted hyperintense lesion in the left insula and inferior frontal lobe. This was confirmed on biopsy as AG and was followed with surveillance imaging. In April 2012, she presented with disease progression and underwent a left temporal lobectomy, with histology showing both AG and grade II astrocytoma. Adjuvant radiotherapy of 50 Gray in 28 fractions was administered. A small area of contrast enhancement appeared in the left parietal lobe in December 2012, which progressed over subsequent months. In June 2013, she underwent a near total excision, with histology showing anaplastic ependymoma. She received six cycles of adjuvant temozolamide. Despite this, the tumour continued to progress, with her seizure control deteriorating, and the development of a right hemiparesis. The patient died in January 2014, aged 19 years.
Article
Angiocentric glioma is a rare subtype of neuroepithelial tumor that is associated with a history of epilepsy. We report a case of cystoid angiocentric glioma associated with an area of calcification. This 25 year old male patient presented with tonic clonic spasm. He underwent craniotomy with complete resection of the lesion. Pathologic specimen showed monomorphous bipolar cells with angiocentric growth pattern.
Chapter
Malignant brain tumors are common solid tumors in the pediatric age group, and the importance of their correct diagnoses cannot be over emphasized. In order to understand these tumors, developmental features of the central nervous system (CNS), and clinical imaging, and their relation to hereditary cancer syndromes must be considered and correlated. The World Health Organization (WHO) Classification is perhaps the most widely used classification for tumors of the CNS. Diagnostic criteria in this chapter reflect those according to the 2007 WHO classification Evolving concepts such as embryonal tumor with multilayered rosette (ETMR) have crested a number of new and previously known tumor entities. Some pediatric brain tumors occur only rarely in adults, and vice versa. Tumors in this chapter are grouped according to cell type into those of the developing central nervous system (CNS), those with features of mature glial and neuronal tissues, and those arising from the choroid plexus, pineal region, sellar region, and meninges. Sellar tumors are not considered in depth, as these are rarely malignant in children. Radiological features correlate with pathological anatomy, and knowledge of both is imperative for accurate diagnosis and treatment.
Article
Full-text available
Mutations of isocitrate dehydrogenase-1 gene (IDH1), most commonly resulting in replacement of arginine at position 132 by histidine (R132H), have been described in World Health Organization grade II and III diffuse gliomas and secondary glioblastoma. Immunohistochemistry using a mouse monoclonal antibody has a high specificity and sensitivity for detecting IDH1 R132H mutant protein in sections from formalin-fixed, paraffin-embedded tissue. Angiocentric glioma (AG), a unique neoplasm with mixed phenotypic features of diffuse glioma and ependymoma, has recently been codified as a grade I neoplasm in the 2007 World Health Organization classification of central nervous system tumors. The present study was designed to evaluate IDH1 R132H protein in AG. Three cases of AG were collected, and the diagnoses were confirmed. Expression of mutant IDH1 R132H protein was determined by immu-nohistochemistry on representative formalin-fixed, paraffin-embedded sections using the antihuman mouse monoclonal antibody IDH1 R132H (Dianova, Hamburg, Germany). Known IDH1 mutation– positive and IDH1 wild-type cases of grade II to IV glioma served as positive and negative controls. All 3 patients were male, aged 3, 5, and 15 years, with intra-axial tumors in the right posterior parietal-occipital lobe, right frontal lobe, and left frontal lobe, respectively. All 3 cases showed characteristic morphologic features of AG, including a monomorphous population of slender bipolar cells that diffusely infiltrated cortical parenchyma and ensheathed cortical blood vessels radially and longitudinally. All 3 cases were negative for the presence of IDH1 R132H mutant protein (0/3). All control cases showed appropriate reactivity. IDH1 R132H mutation has been described as a common molecular signature of grade II and III diffuse gliomas and secondary glioblastoma; however, AG, which exhibits some features of diffuse glioma, has not been evaluated. The absence of mutant IDH1 R132H protein expression in AG may help further distinguish this unique neoplasm from diffuse glioma.
Article
Full-text available
Ependymomas are glial neoplasms whose clinical behavior is difficult to predict based on histology alone. Recently, a comparative genomic hybridization study identified frequent chromosome 9p and 13q losses in anaplastic ependymomas, suggesting that p16 and RB alterations may be involved in tumor progression. In order to test this hypothesis further, 101 myxopapillary, conventional, and anaplastic ependymomas (51 spinal and 50 intracranial tumors) were tested for RB and p16 deletions using fluorescence in situ hybridization. Clinical follow-up, ranging from 2 to 198 months (median 46 months), was obtained in 90 cases (91%). RB and p16 deletions were seen in 22 of 92 (24%) and 22 of 89 (25%) informative cases, respectively. Polysomies were more frequent in the grade I and II spinal tumors, consistent with prior reports of increased aneuploidy in such cases. No significant genetic associations were seen with tumor grade, recurrence, or death, suggesting that 9p and 13q deletions do not play a prominent role in the malignant progression of ependymomas, as has been implicated in other glioma subtypes.Keywords: brain tumor, ependymoma, tumor genetics, FISH, p16/RB, RB pathway, prognosis
Article
Full-text available
Angiocentric glioma was recently recognized as a distinct clinicopathological entity in the 2007 World Health Organization classification of tumors of the central nervous system. Typically, it presents with seizure in children and young adults. However, our patient did not have a history of seizure. Seizure did not occur up to 6 months after operation. Although it usually does not have calcification brain magnetic resonance imaging in our patient showed T1-hyperintense and T2-hypointense signals with calcification.
Article
Full-text available
Supratentorial cortical ependymomas (CE) are rare, with 7 cases reported. The lesions, typically occurring in the superficial cortex in young adults and associated with a history of seizures, are not fully characterized. Furthermore, their relationship with the recently described angiocentric glioma (AG) is still being debated. This study was undertaken to summarize the authors' experience with CEs. Between 1997 and 2009, 202 cases of ependymoma were surgically treated at the Mayo Clinic, 49 of which were supratentorial. Among these, 9 CE cases were retrospectively identified. Clinical, imaging, and pathological features of each case were reviewed. Tumors arose from the frontal (5 cases), parietal (3), and occipital (1) lobes. No tumor occurred in the temporal lobe, despite its reported association with seizures. The mean age at presentation was 27 ± 19 years (± SD) and age at resection was 36 ± 16 years. The mean size of the lesion was 16 ± 14 cm(3). Seizures were the presenting symptom in 78%. Cross-sectional imaging in 8 cases was characterized by a heterogeneous mass with multiple cystlike areas and enhancement of the soft-tissue component. Gross-total resection was achieved in 8 of 9 tumors. Pathologically, 6 were low-grade (WHO Grade II) and 3 were anaplastic (WHO Grade III) ependymomas. All tumors exhibited the focal presence of perivascular pseudorosettes, but only 1 (11%) exhibited the focal presence of a true rosette. A bipolar spindle cell component resembling AG was present in 3 (33%) and "Schwannian-like" nodules in 2 (22%). Subpial aggregation and peripheral infiltration were present in 4 cases (44%). With a mean postsurgery follow-up of 62 ± 38 months, only 2 lesions recurred locally after imaging-confirmed gross-total resection, both being Grade III. In 5 (71%) of 7 patients presenting with seizures an Engel Class I outcome was achieved. Cortical ependymomas represent a rare type of ependymoma occurring superficially in the cortex. Morphologically, these tumors are protean, varying from classic to epithelioid, clear cell, and tanycytic. Some also exhibited features typical of AG. Most tumors were low grade and cured with resection. Anaplastic tumors occur and may recur locally despite provision of radiation therapy. Cortical ependymomas frequently, but not always, present with seizures, but despite their high association with epilepsy, none occurred in the temporal lobe in any of the authors' 9 patients. Overall, CEs appear to have a relatively favorable prognosis compared with other supratentorial ependymomas.
Article
Mutations of isocitrate dehydrogenase-1 gene (IDH1), most commonly resulting in replacement of arginine at position 132 by histidine (R132H), have been described in World Health Organization grade II and III diffuse gliomas and secondary glioblastoma. Immunohistochemistry using a mouse monoclonal antibody has a high specificity and sensitivity for detecting IDH1 R132H mutant protein in sections from formalin-fixed, paraffin-embedded tissue. Angiocentric glioma (AG), a unique neoplasm with mixed phenotypic features of diffuse glioma and ependymoma, has recently been codified as a grade I neoplasm in the 2007 World Health Organization classification of central nervous system tumors. The present study was designed to evaluate IDH1 R132H protein in AG. Three cases of AG were collected, and the diagnoses were confirmed. Expression of mutant IDH1 R132H protein was determined by immunohistochemistry on representative formalin-fixed, paraffin-embedded sections using the antihuman mouse monoclonal antibody IDH1 R132H (Dianova, Hamburg, Germany). Known IDH1 mutation-positive and IDH1 wild-type cases of grade II to IV glioma served as positive and negative controls. All 3 patients were male, aged 3, 5, and 15 years, with intra-axial tumors in the right posterior parietal-occipital lobe, right frontal lobe, and left frontal lobe, respectively. All 3 cases showed characteristic morphologic features of AG, including a monomorphous population of slender bipolar cells that diffusely infiltrated cortical parenchyma and ensheathed cortical blood vessels radially and longitudinally. All 3 cases were negative for the presence of IDH1 R132H mutant protein (0/3). All control cases showed appropriate reactivity. IDH1 R132H mutation has been described as a common molecular signature of grade II and III diffuse gliomas and secondary glioblastoma; however, AG, which exhibits some features of diffuse glioma, has not been evaluated. The absence of mutant IDH1 R132H protein expression in AG may help further distinguish this unique neoplasm from diffuse glioma.
Article
To determine if histograms of apparent diffusion coefficients (ADC) can be used to differentiate paediatric brain tumours. Imaging of histologically confirmed tumours with pre-operative ADC maps were reviewed (54 cases, 32 male, mean age 6.1 years; range 0.1-15.8 years) comprising 6 groups. Whole tumour ADC histograms were calculated; normalised for volume. Stepwise logistic regression analysis was used to differentiate tumour types using histogram metrics, initially for all groups and then for specific subsets. All 6 groups (5 dysembryoplastic neuroectodermal tumours, 22 primitive neuroectodermal tumours (PNET), 5 ependymomas, 7 choroid plexus papillomas, 4 atypical teratoid rhabdoid tumours (ATRT) and 9 juvenile pilocytic astrocytomas (JPA)) were compared. 74% (40/54) were correctly classified using logistic regression of ADC histogram parameters. In the analysis of posterior fossa tumours, 80% of ependymomas, 100% of astrocytomas and 94% of PNET-medulloblastoma were classified correctly. All PNETs were discriminated from ATRTs (22 PNET and 4 supratentorial ATRTs) (100%). ADC histograms are useful in differentiating paediatric brain tumours, in particular, the common posterior fossa tumours of childhood. PNETs were differentiated from supratentorial ATRTs, in all cases, which has important implications in terms of clinical management. Key Points • MR based apparent diffusion coefficient histograms can help differentiate paediatric brain tumours • ADC histogram parameters correctly classified the great majority of posterior fossa tumours.
Article
Angiocentric glioma (AG) is an epileptogenic benign cerebral tumor primarily affecting children and young adults, and characterized histopathologically by an angiocentric pattern of growth of monomorphous bipolar cells with features of ependymal differentiation (WHO grade I). We report an unusual cerebral glial tumor in a 66-year-old woman with generalized tonic-clonic seizure; the patient also had a 6-year history of headache. On MRI, the tumor appeared as a large T2-hyperintense lesion involving the right insular gyri-anterior temporal lobe, with post-contrast enhancement in the insula region. Histopathologically, the tumor involving the insular cortex-subcortical white matter was composed of GFAP-positive glial cells showing two different morphologies: one type had monomorphous bipolar cytoplasm and was angiocentric with circumferential alignment to the blood vessels, with dot-like structures positive for epithelial membrane antigen and a Ki-67 labeling index of <1%, and the other was apparently astrocytic, being diffusely and more widely distributed in the parenchyma, showing mitoses and a Ki-67 labeling index of >5%. In the anterior temporal lobe, a diffuse increase in the number of astrocytic cells was evident in part of the cortex and subcortical white matter. On the basis of these findings, we considered whether the present tumor may represent an unusual example of AG with infiltrating astrocytic cells showing primary anaplastic features (AG with anaplastic features), or anaplastic astrocytoma showing primary vascular-associated ependymal differentiation (anaplastic astrocytoma with angiocentric ependymal differentiation). At present, the latter appears to be the more appropriate interpretation.
Article
Angiocentric glioma (AG) is a rare central nervous system (CNS) neoplasm that was only recently recognized by the World Health Organization (WHO). AG occurs in a broad age range, shows no gender predilection, and arises superficially in the cerebrum, usually resulting in medically intractable seizures. Most cases are cured by surgical excision alone, consistent with a WHO grade I neoplasm. We report a case of an AG in the right frontal lobe of a 57-year-old female, emphasizing the cytologic and immunohistochemical features, including confirmation and comparison with the surgical specimen. To our knowledge, this is the first report detailing the cytology of AG, including demonstration of important diagnostic findings that were only appreciated in the cytologic preparations and not in the smears or the surgical specimen. We also compare and contrast AG to other entities in the differential diagnosis and include a review of the literature.