Journal of Clinical Neuroscience 21 (2014) 1310–1314

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Journal of Clinical Neuroscience

journal homepage: www.elsevier.com/locate/jocn

Clinical Study

Primary intracranial haemangiopericytoma: Comparison of survival

outcomes and metastatic potential in WHO grade II and III variants
Omprakash Damodaran a,e,⇑, Peter Robbins b, Neville Knuckey a,c, Michael Bynevelt d, George Wong a,
Gabriel Lee a,c
a
Department of Neurosurgery, Sir Charles Gairdner Hospital, Perth, WA, Australia
b
Department of Pathology (PATHWEST), Sir Charles Gairdner Hospital, Perth, WA, Australia
c
School of Surgery, University of Western Australia, WA, Australia
d
Neurological Intervention and Imaging Service (WA), Sir Charles Gairdner Hospital, Perth, WA, Australia
e
Department of Neurosurgery, Liverpool Hospital, Elizabeth Street, Liverpool, NSW 2170, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Primary intracranial haemangiopericytomas (HPC) are rare, highly vascular tumours with a high propen-
Received 18 May 2013 sity for local recurrence and distant metastasis. Optimal treatment includes maximal surgical resection
Accepted 13 November 2013 followed by adjuvant radiotherapy. In 2007, new histopathological grading criteria were introduced to
differentiate between high grade (World Health Organization [WHO] grade III) and low grade (WHO
grade II) tumours. Given the rarity of this tumour, there is a paucity of information regarding the prog-
Keywords: nostic significance of histological grade. We conducted a retrospective review of our 20 year experience
Grade
in treating 27 patients with HPC at our institution. Statistical analysis to compare overall survival, local
Haemangiopericytoma
High grade
recurrence rate and metastatic potential between the two grades were conducted using Kaplan–Meier
Local recurrence analysis. The estimated median survival for grade II HPC was 216 months and for grade III tumours
Low grade was 142 months. On multivariate analysis, grade II tumours were associated with better survival than
Metastasis grade III lesions (hazard ratio = 0.16, 95% confidence interval 0.26–0.95; p = 0.044). During the study per-
iod, 33% of grade III tumours developed local recurrence compared to 21% of grade II tumours. Metastases
were found in 36% of grade II patients and 25% of grade III patients. There was no significant statistical
difference in local recurrence rate and metastasis between the two grades. Higher histological grading
in HPC is associated with worse overall survival. However based on our series higher histological grading
is not associated with higher local recurrence or distant metastatic rates.
Ó 2014 Elsevier Ltd. All rights reserved.

1. Introduction peripheral metastasis approaching nearly 50% [1,4,5]. The role of

Primary intracranial haemangiopericytomas (HPC) are rare,
highly vascular tumours with a high propensity for local recur-
rence and distant metastasis [1]. They originate from pericytes
around capillaries and account for less than 1% of all intracranial
tumours [2]. They share a common arachnoidal location with
meningiomas [1]. Establishing a preoperative diagnosis can be
challenging, as most radiological features are similar to those
typically associated with meningiomas [3]. Optimal treatment
includes maximal surgical resection followed by adjuvant
radiotherapy [1,2]. Despite this, previous studies have reported
local recurrence rates between 30% to 90% and a 15 year risk of
⇑ Corresponding author. Tel.: +61 2 9828 3000; fax: +61 2 96491 4131.
E-mail address: domprakash@hotmail.com (O. Damodaran).
chemotherapy is limited with HPC, but has been indicated in the
treatment of peripheral metastatic disease [4].
HPC were previously classified as ‘‘angioblastic meningiomas’’.
Its unique characteristics led the World Health Organization
(WHO) to reclassify HPC as a separate entity in 1993. In 2007,
new histopathological grading criteria were introduced to differen-
tiate between high grade (WHO grade III) and low grade (WHO
grade II) tumours. This concept was adopted from a large series
on meningeal HPC published by Mena et al. in 1991 [6]. Given
the rarity of this tumour and the recent introduction of the WHO
grading scheme, there is very little information regarding the prog-
nostic significance of histological grade and rationale for long term
monitoring. In this paper, the authors report their 20 year experi-
ence in treating 27 patients with HPC at our institution. This paper
aims to provide a long term comparative analysis and experience
in both grade II and grade III intracranial HPC.

http://dx.doi.org/10.1016/j.jocn.2013.11.026
0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.
 O. Damodaran et al. / Journal of Clinical Neuroscience 21 (2014) 1310–1314
2. Methods
Patients diagnosed with HPC between 1989 and 2011 were
identified by performing a computer search of a prospectively
maintained database within the Department of Neurosurgery at
Sir Charles Gairdner Hospital, Australia. Histopathology reports
were verified to confirm the diagnosis of HPC. Relevant clinical,
surgical and radiological data were collected by retrospective chart
review. Information recorded included details of surgical treat-
ment, adjuvant therapy, postoperative complications, local or
distant recurrence, and peripheral metastasis at most recent
follow-up. Extent of resection was quantified as gross total
resection (GTR) or subtotal resection. Extent of tumour resection
was established from operative notes and was defined as ‘‘gross to-
tal’’ after verification with available postoperative imaging (CT
scan or MRI). Where there was insufficient information to confirm
the extent of resection, it was documented as ‘‘unable to quantify’’.
HPC diagnosed prior to 2007 were not graded. Based on the
WHO 2007 classification guidelines tumours with anaplastic fea-
tures were designated as grade III. Features of anaplasia include
high mitotic activity (more than five mitoses per 10 high power
fields) and/or necrosis, plus at least two of haemorrhage, moderate
to high nuclear atypia, and cellularity [7]. For the purposes of this
study, all pathology slides were independently reviewed by an
experienced neuropathologist (P.R.) who was blinded to the
clinical and survival data of individual patients.
Overall survival was calculated from the time of initial surgery
to death or the date of last known post-treatment follow-up.
Histopathology grading was unable to be performed in one patient,
hence they were excluded from survival and comparative analysis.
Local recurrence was defined as unequivocal evidence supporting
tumour growth in the postoperative site on imaging. Peripheral
metastasis was deemed to be present if symptomatic lesions in
extra-central nervous system sites were confirmed by imaging
studies. Neuroaxis metastasis denoted new tumour development
in the brain or spine distant from the primary operative site.
Statistical analysis of overall survival was conducted using the
Kaplan–Meier product-limit method with confidence interval (CI)
at 95% and the significant p value was set below 0.05. A Cox pro-
portional hazards regression analysis was conducted to determine
the factors associated with cause-specific survival. The chance for
interaction between variables was further checked using a back-
ward stepwise regression. Statistical analysis was conducted using
the Statistics Package for the Social Sciences version 20 (SPSS,
Chicago, IL, USA).
3. Results
A total of 27 patients with HPC were treated at our institution
from 1989 to 2011. The median age of the 12 men and 15 women
was 42 years (range 25–82 years). Supratentorial tumours were
the most common, accounting for 76% of all cases. Most of these
lesions (42%) were found in a parasagittal location. Posterior fossa
and spine locations accounted for 12% and 4% of tumours, respec-
tively. Two patients (7.4%) underwent preoperative cerebral
angiogram and embolisation of arterial feeders prior to surgery
due to radiological features of hypervascularity on MRI.
Pathological diagnosis of HPC was made by identifying typical
features such as branching ‘‘staghorn’’ vasculature, widespread
staining for reticulin and absence of staining for epithelial
membrane antigen [1,8]. Based on WHO 2007 criteria, 12 (44.4%)
patients were assessed as grade III and 14 patients (52%) were
classified as having grade II HPC.
1311
3.1. Treatment
All patients underwent surgical resection. In total, 23 patients
(85%) achieved GTR and two patients (7.5%) had subtotal resection.
The extent of resection was unable to be quantified from operative
notes in two patients. These two patients had their surgery at least
18 years ago and postoperative imaging data were not available.
Early in the surgical series, one patient died in the early postoper-
ative period due to severe blood loss. This patient was excluded
from subsequent statistical analysis of data. One patient under-
went a two stage procedure to achieve GTR after severe blood loss
was encountered during the first stage of surgery. A cerebral angio-
gram was undertaken and arterial feeders were embolised prior to
the subsequent surgery to excise the residual disease (estimated to
be 30% of original tumour volume).
Early external beam radiotherapy to the peri-resection zone
(dose ranges 48 to 60 Gy) was administered to 63% (17/27) of
patients following initial surgery. Two patients who had early
external beam radiotherapy also received stereotactic radiosurgery
for a subsequent small recurrence. In the remaining patients, 50%
(5/10) who had not received radiotherapy treatment following
their initial surgery subsequently received adjuvant radiotherapy
for the first recurrence after surgery.
3.2. Survival
Patients were followed up by both the neurosurgical and radia-
tion oncology teams in their respective clinics. All patients were
seen within 3 months of surgery and had regular clinic visits with
either annual or bi-annual follow-up brain imaging performed. Ele-
ven patients (including one early postoperative death) died during
the follow-up period. The median overall survival for all patients
was 216 months (Fig. 1). The overall survival rates at 5, 10, 15
and 20 years were 79%, 56%, 44% and 22%, respectively. The esti-
mated median survival for grade II HPC was 216 months and for
grade III HPC was 142 months (Fig. 2). On multivariate analysis,
grade II tumours were associated with better survival than grade
III lesions (hazard ratio [HR] = 0.16, 95% CI 0.26–0.95; p = 0.044)
(Fig. 2, Table 1). Patient age did not impact survival, but male sex
was associated with better survival (HR = 0.097, 95% CI 0.013–
0.73; p = 0.023) (Fig. 2, Table 1). Neither the presence of peripheral
metastasis nor local recurrence was significantly associated with
poorer survival rates. Treatment variables such as GTR and adju-
vant radiotherapy were also not associated with better survival.
3.3. Local recurrence
The local recurrence rate in our series was 28% (7/25) at a med-
ian follow-up period of 172.5 months (14.4 years). The 5, 10 and
15 year recurrence rates were 20%, 54% and 77%, respectively. In
the study period, 55.6% (5/9) of patients who did not receive early
adjuvant radiotherapy developed local recurrence. By comparison,
only 12.5% (2/16) of patients who received adjuvant radiotherapy
developed local recurrence. On multivariate analysis, early adju-
vant radiotherapy following the first surgery was associated with
reduction in local recurrence (HR = 0.071, 95% CI 0.007–0.70;
p = 0.023). During the study period, 33% of grade III tumours
developed local recurrence compared to 21% of grade II tumours.
However, a higher histological grade was not statistically associ-
ated with increased risk of local recurrence (p = 0.52).
3.4. Metastasis
In this series, 32% (8/25) of patients developed symptomatic
peripheral metastasis during a median follow-up period of
204.6 months. Neuroaxis metastasis was noted in 12% (3/25) of
1312 O. Damodaran et al. / Journal of Clinical Neuroscience 21 (2014) 1310–1314

Fig. 1. Kaplan–Meier survival curve demonstrating survival after the initial diagnosis of haemangiopericytoma (median overall survival 216 months). Cum = cumulative.

Fig. 2. Kaplan–Meier survival curve demonstrating the shorter survival in grade III haemangiopericytoma compared to grade II after the first surgery. Cum = cumulative,
WHO = World Health Organization.

patients. The peripheral metastasis rates at 5, 10 and 15 years were 4. Discussion

10%, 31% and 77%, respectively. The most common sites for periph-
eral metastasis were lung, liver and bone. Bony metastases were
most frequently documented in the pelvis, spine and scapula.
Metastases were found in 36% of grade II patients and 25% of grade
III patients, but this difference did not reach statistical significance
(p = 0.36). Other variables such as extent of resection, adjuvant
radiotherapy and age also did not have any significant association
with peripheral metastasis.
HPC are aggressive tumours with high propensity for local
recurrence and distant metastasis after a prolonged symptom-free
period [9]. In this series we present a long term comparative anal-
ysis of grade II and grade III HPC over an extended median follow-
up period of 14 years.
Our experience has shown that surgical resection of these
tumours can be challenging due to their hypervascularity. One
patient died due to severe blood loss early in the series. In another
 O. Damodaran et al. / Journal of Clinical Neuroscience 21 (2014) 1310–1314
Table 1
A comparison of grade II and grade III haemangiopericytomas
Grade II Grade III
Number of patients 14 (52%) 12 (44.4%)
Median age 43.5 years 36 years
Female sex 35.7% (5/14) 58.3% (7/12)
Surgery
Gross total resection 93% (13/14) 75% (9/12)
Subtotal resection, greater than 50% 0 16.7% (2/12)
Unable to quantify resection 7% (1/14) 8.3% (1/12)
Adjuvant radiotherapy 64% (9/14) 66.7% (8/12)
Local recurrence 21% (3/14) 33% (4/12)
Peripheral metastasis 36% (5/14) 25% (3/12)
Overall median survival 216 months 142 months
patient, the surgery was staged due to extensive blood loss.
Preoperative embolisation can minimise intraoperative blood loss
as demonstrated by this latter patient, where blood loss encoun-
tered during the second surgery was insignificant compared to
her primary surgery.
Previous studies have demonstrated a correlation between GTR
and improved survival. The GTR rates reported in the literature
vary between 50–83.3% [2,3,10]. In our series, 85% of patients
had GTR and only 7.5% had subtotal resection. The higher survival
noted in our study could be due to a greater proportion of patients
undergoing GTR. The median survival in our series was
216 months (mean 205 months) and the reported mean survival
in the literature varies between 84–216 months. The survival rates
at 5, 10 and 15 years after diagnosis were 79%, 56% and 44%,
respectively. In comparison, Guthrie et al. estimated the median
survival rates at 5, 10 and 15 years after surgery to be 67%, 40%
and 23%, respectively based on their series [11]. While it is rare,
long term survival is also well recognised. One patient in this series
survived up to 27 years after diagnosis. Bassiouni et al. also
reported a patient surviving for 30 years after diagnosis [2].
Radiotherapy appears to reduce local recurrence and improve
overall survival. Guthrie et al. noted an improvement in the mean
time to recurrence after radiotherapy increased from 34 to
75 months [11]. Dufour et al. also observed a decrease in local
recurrence rate with external beam radiotherapy with no effect
on distant metastasis [12]. However, the literature analysis by
Rutkowski et al. found no statistically significant increase in
survival among patients undergoing GTR and radiotherapy when
compared to those with GTR alone [13]. In the current study,
adjuvant radiotherapy did not alter overall survival or incidence
of peripheral metastasis, but was associated with reduction in local
recurrence.
Since the WHO reclassification of HPC in 2007, there has been
very few recent studies examining the difference in outcomes be-
tween the two grades of HPC. In their large series of patients, Mena
et al. noted a significantly better survival for differentiated HPC
(grade II, 144 months) when compared to anaplastic HPC (grade
III, 62 months) [6]. Prior to this, Ecker reported an increased risk
of recurrence with high grade tumours but histological grading
had no overall effect on survival [14]. Mena et al. has also associ-
ated higher grade with increased risk of recurrence and distant
metastasis [6]. Other authors report high grade tumours to recur
36–80.4 months earlier than low grade tumours [14,15]. In the cur-
rent study, patients with grade II variants had significantly im-
proved survival compared to grade III patients (216 versus
142 months, p = 0.044). However there was no significant associa-
tion between higher grade and increased risk of local recurrence
and metastasis.
The incidence of local recurrence increases with the length of
follow-up. In the current surgical series the 5, 10 and 15 year
recurrence rates were 20%, 54% and 77%, respectively. At
1313
comparable time intervals, Guthrie et al. reported recurrence rates
of 65%, 76%, and 87%, respectively [11]. Interestingly, Guthrie et al.
further noted that after the first recurrence the subsequent
recurrences happened at shorter intervals [11]. The lower recur-
rence rates in our study could be related to a higher GTR rate in
comparison to Guthrie’s series (85% versus 55%). These results
suggest that patients require life-long surveillance despite gross
surgical resection, as the chance of recurrence is high with long
term follow-up.
Similarly, the incidence of metastatic disease increases with the
duration of follow-up. The most common extra-neural metastatic
sites in order of decreasing frequency are bones, liver, lungs,
abdominal cavity, lymph nodes, skeletal muscle, kidney, pancreas
and skin [3]. The extra-neural metastatic rate was 32% in our series
and 12% developed metastasis in the brain and spine distant from
the operative site. The peripheral metastasis rates at 5, 10 and
15 years were 10%, 31% and 77%, respectively. Guthrie et al. re-
ported the probability of metastasis at 5, 10 and 15 years to be
13%, 33% and 64%, respectively [11]. Metastasis has been reported
to occur as early as 7 months and as late as 20 years after diagnosis.
This confirms the unpredictable and highly malignant nature of
HPC. Hence, long term follow-up clinical examinations to rule
out metastasis must be performed at regular intervals. Regular
chest radiographs at a 6 to 12 monthly interval is an inexpensive
option with follow-up CT scan if any there is any suspicion of pul-
monary metastasis [6]. Any report of bony pain needs to be inves-
tigated carefully with imaging [6].
The main limitation of this study is its retrospective nature.
However large prospective studies are difficult to design given
the rarity of this tumour. This series demonstrates that in current
clinical practice GTR is the initial management of choice. Postoper-
ative radiotherapy is not uniformly administered and its use will
be dependent on various factors, including age, grade, and extent
of resection, as well as patient and physician choices. This study
also adds further evidence to previous reports with regards to
grade and survival and the beneficial effects of radiotherapy in pre-
venting local recurrence.
5. Conclusion
HPC are a challenging clinical entity given their unpredictable
characteristic of local recurrence and distant metastasis decades
after initial diagnosis. The probability of local recurrence and dis-
tant metastasis increases with time, even after a long period of la-
tency. This study confirms the heterogeneous behaviour of this
tumour and the need for aggressive surgical resection. We have
demonstrated the association between higher histological grading
and worse overall survival. However histological grading and its ef-
fect on local recurrence and distant metastasis still requires further
investigation through large multi-centre studies to reach statistical
significance. Neurosurgeons and radiation oncologists should be
vigilant and obtain a complete systems history and perform a thor-
ough physical examination to rule out metastasis at every opportu-
nity. We advocate close and life-long follow-up of these patients
with imaging at regular intervals even during a symptom-free
period.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other con-
flicts of interest in relation to this research and its publication.
Acknowledgements
We thank Ms Charley Budgeon (biostatistician, Sir Charles
Gairdner Hospital) for her assistance.
1314 O. Damodaran et al. / Journal of Clinical Neuroscience 21 (2014) 1310–1314

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