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Original Article

An Underlying Pathological Mechanism of Meningiomas with Intratumoral Hemorrhage:


Undifferentiated Microvessels
Hong-Cai Wang1,2, Bo-Ding Wang2, Mao-Song Chen2, Shi-Wei Li2, Hai Chen2, Wei Xu2, Jian-Min Zhang1

- BACKGROUND: Meningiomas usually present with a - CONCLUSIONS: Our results suggest that tumor vascu-
gradual onset of symptoms, and their acute presentation lature in meningiomas is heterogeneous, and that the
with a hemorrhagic event appears to be a rare condition. undifferentiated vessels may play a pivotal role in the
Although many clinical features of such a condition have spontaneous intratumoral hemorrhage from meningiomas.
been characterized, pathophysiological mechanisms under-
lying the bleeding remain unclear, and some contradictory
results have been reported. The value of tumor vascularity
as an index for the bleeding propensity of meningiomas is
inconsistent. We sought to identify whether meningiomas INTRODUCTION
have different types of blood vessels, and to explore the
association of the different tumor vessels with intratumoral
hemorrhage.
- METHODS: Six patients with meningioma with acute
M eningiomas, the most common benign intracranial
tumors, were first described by Felix Plater in 1614 and
reported in detail by Harvey Cushing in 1938.1 Although
meningiomas encompass a broad spectrum of symptoms and
signs, their acute presentation with a hemorrhagic onset appears
onset due to intratumoral hemorrhage were identified, and to be a rare event.2,3 The rarity of this condition not only makes
12 nonhemorrhagic meningiomas were matched according determining causative factors of the hemorrhage challenging, but
to specific clinical data. The characteristics of tumor also makes the mechanism of spontaneous hemorrhage harder to
vessels were examined through immunohistochemical understand.2-4 Nonetheless, because the mainstay of treatment is
staining of CD31, CD34, and smooth muscle actin (SMA). early surgical evacuation, prompt diagnosis of this rare category
of intracranial hemorrhage is imperative. Owing to the high
The number of stained vessels was counted and compared
morbidity associated with hemorrhagic meningiomas, especially
between the 2 groups.
in patients with sudden onset of coma, and their still ambiguous
- RESULTS: Two distinct types of blood vessels were bleeding mechanisms, a more complete understanding of this
determined in all meningiomas: undifferentiated (CD31D/ condition is needed.
CD34L) and differentiated (CD31D/CD34D) vessels, and According to previously reported cases, the reported incidence
of spontaneous meningioma hemorrhage ranges from approxi-
most differentiated vessels were covered by pericytes
mately 0.5% to 2.4%.2,5 The reason for the low rate of this event in
marked by SMA. However, only the mean number of un-
such highly vascularized tumors is not well understood. Fortu-
differentiated vessels in hemorrhagic meningiomas was nately, the body of information on these tumors has been
significantly higher than that in controls (15.3  4.9 vs. 6.4 growing, especially over the past several decades. Bosnjak et al.2
 3.6; P < 0.01). Neither the number of differentiated ves- reviewed 145 literature-derived cases and identified 3 main fac-
sels nor the total number of tumor vessels were signifi- tors associated with an increased propensity for hemorrhage in
cantly different between the 2 groups (P > 0.05). meningiomas: intraventricular and convexity location, fibrous

Key words From the 1Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang
- CD31 University School of Medicine, Hangzhou; and 2Department of Neurosurgery, Li Hui Li
- CD34 Hospital of Medical Center of Ningbo, Ningbo, China
- Hemorrhage To whom correspondence should be addressed: Jian-Min Zhang, M.D., Ph.D.
- Mechanism [E-mail: zjm135zjm135@163.com]
- Meningiomas Citation: World Neurosurg. (2016) 94:319-327.
http://dx.doi.org/10.1016/j.wneu.2016.07.042
Abbreviations and Acronyms
Journal homepage: www.WORLDNEUROSURGERY.org
CT: Computed tomography
H&E: Hematoxylin and eosin Available online: www.sciencedirect.com
MRI: Magnetic resonance imaging 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
SMA: Smooth muscle actin

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HONG-CAI WANG ET AL. UNDIFFERENTIATED MICROVESSELS IN MENINGIOMAS WITH INTRATUMORAL HEMORRHAGE

histopathology, and age >70 years or <30 years.2 The most meningiomas are highly vascularized tumors, and they are
pathophysiological mechanisms underlying the bleeding remain graded mainly according to the mitotic index, not according to
poorly defined, however, and the role of intratumoral tumor vasculature.
vasculature in spontaneous hemorrhage from meningiomas is
still controversial.2,3 Some reports have suggested a positive cor- Immunohistochemistry and Quantification of Stained Vessels
relation between the intratumoral vasculature and meningioma Along with routine immunohistochemical examination for the
hemorrhage,6-8 but other studies have found no significant tumor diagnosis, classification, and grading, immunohistochem-
correlation.3,9-11 ical staining of CD31, CD34, and SMA was performed to identify
This apparent discrepancy may be explained in part by the fact the different types of blood vessels related to the vascular differ-
that the tumor vasculature is heterogeneous, and different studies entiation and maturation. We used the following primary anti-
have not applied the same vascular marker. Varying characteristics bodies: mouse anti-human endothelial cell CD31 monoclonal
of blood vessels have been identified in prostate cancer, lung antibody (1:200; Dako, Glostrup, Denmark), mouse anti-human
cancer, and renal cell carcinoma through various vascular endothelial cell CD34 monoclonal antibody (1:100; Dako), and
markers.12-14 For example, 2 distinct types of blood vessels have rabbit anti-human pericyte SMA monoclonal antibody (1:200;
been identified in renal cell carcinoma: undifferentiated (CD31þ/ Abcam, Cambridge, UK). Six consecutive slides of 1 tissue block
CD34) and differentiated (CD31þ/CD34þ) vessels. Most impor- were used for staining, including 2 slides for CD31, 2 for CD34,
tantly, only the undifferentiated vessels had a significant correla- and 2 for SMA. Immunohistochemical staining was performed
tion with higher tumor grades.14 Although these studies did not with standard reagents and techniques using a sensitive
examine the relationship between tumor vascularity and streptavidin-biotinylated horseradish peroxidase complex system
spontaneous intratumoral hemorrhage, their results indicate that according to the manufacturer’s instructions. To control for
different types of tumor vessels have distinct implications and nonspecific binding of the secondary antibody to endogenous sites
significance. Based on these compelling results and our detailed within the tissue, immunohistochemical controls were performed
clinical data, we sought to determine whether meningiomas also in which the primary antibody was omitted.
contain different types of blood vessels in terms of vascular The technique for counting stained blood vessels was modified
differentiation, and then to explore the associations of these from the criteria used in previous studies.14-16 First, 3 separated
different types of vessels with intratumoral hemorrhage. tumor regions with the greatest density of positive endothelial
cells (hotspots) were circled on 1 slide to identify the tumor
METHODS vascularity. For evaluation of the discrepant expression of CD31
and CD34 in these consecutive tissue sections, the hotspot was
Study Population and Tissue Specimens defined by the most highly vascularized area in 1 CD31-stained
After obtaining Institutional Ethics Board approval, we retro- slide. The same regions were circled on the other consecutive
spectively reviewed the charts of 271 patients with meningiomas slides to ensure that stained vessels in the same regions on each
who underwent craniotomy for tumor resection at the Li Hui Li slide were counted. Then the immunoreactive blood vessels in 1
Hospital of the Medical Centre of Ningbo between July 2008 and separated region were counted in 3 consecutive microscopic fields
December 2015. Six of these 271 patients presented with an acute at a magnification of 200. The mean number of vessels counted
spontaneous intratumoral hemorrhage. In this study, intratumoral in the selected areas of 2 sections stained with the same marker
hemorrhage comprises 2 types of bleeding: solitary intratumoral was recorded as the vascular density. Any brown-staining endo-
hemorrhage and combined intra/extratumoral hemorrhage. The thelial cell or endothelial cell cluster that was clearly separated
extratumoral hemorrhage should be secondary to intratumoral from adjacent vessels, tumor cells, and connective elements was
bleeding (Figure 1). Twelve patients with nonhemorrhagic considered a single, countable vessel regardless of whether a
meningiomas matched according to sex, histological subtype, vessel lumen was seen.
and lesion location served as a comparison group. No patient
had evidence of bleeding tendency or other predisposing factors Statistical Analysis
for hemorrhage, such as receipt of antiplatelet or anticoagulant All continuous data are expressed as mean  standard deviation.
medication. Patients without available tissue blocks or slides for Statistical analyses were performed with SAS version 8.1 (SAS
analysis were excluded from this study. Institute, Cary, North Carolina, USA), and Student’s t test
Formalin-fixed, paraffin-embedded tissue specimens were was used for comparison analysis. Differences were considered
consecutively sectioned into 4-mm-thick sections for routine he- significant at P < 0.05.
matoxylin and eosin (H&E) staining and immunohistochemical
evaluation. Sections were reviewed by 2 independent pathologists RESULTS
under light microscopy, and the diagnosis was reconfirmed and
classified according to histological anaplasia as benign (grade I), Clinical and Histological Features
atypical with incipient signs of anaplasia (grade II), or overtly Among the 271 patients with meningiomas who underwent
anaplastic (grade III). This grading corresponds in essence to the surgical treatment, 6 (2.2%) had a significant intratumoral
2007 World Health Organization classification system. However, hemorrhage and an accurate diagnosis provided by histopatho-
the meningiomas were not further divided into subgroups by logical examination. The clinical features of these 6 patients are
grade in this study. Along with the fact that there was an insuf- summarized in Table 1. All 6 patients experienced a stroke-like
ficient number of cases to create subgroups for statistical analysis, episode characterized by the sudden onset of acute headache,

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ORIGINAL ARTICLE
HONG-CAI WANG ET AL. UNDIFFERENTIATED MICROVESSELS IN MENINGIOMAS WITH INTRATUMORAL HEMORRHAGE

Figure 1. Illustration of different types of intratumoral hemorrhage from type combined intratumoral hemorrhage with extratumoral hemorrhage,
meningiomas. (A) A meningioma located in the left temporal region. (BeF) and the extratumoral hemorrhage originated from intratumoral bleeding
There were 2 bleeding types of intratumoral hemorrhage in this study. One (CeF).
bleeding type was solitary intratumoral hemorrhage (B). The other bleeding

nausea and vomiting, vertigo, hemiparesis, and/or altered con- Correspondingly, 2 patients had a solitary intratumoral
sciousness. The group included 4 women and 2 men, ranging in hemorrhage only, and 4 patients had combined intratumoral
age from 39 to 65 years (mean, 51.8  9.1 years). On radiologic and extratumoral hemorrhage; abnormal blood vessels, such as
images, the hemorrhagic meningiomas were located at the aneurysms or vascular anomalies, were not detected on further
convexity in 3 patients, in parasagittal areas in 2 patients, and in examination by CT angiography or magnetic resonance
the falx in 1 patient. Computed tomography (CT) and magnetic venography (Figure 3). The 2 cases illustrated in Figures 2 and
resonance imaging (MRI) showed well-defined, dense, con- 3 represent the 2 different types of intratumoral hemorrhage.
toured extra-axial masses displacing the adjacent brain and had The diameter of these lesions ranged from 31 mm to 65 mm
acute or subacute intratumoral hemorrhage; intratumoral hem- (mean, 45.8  11.8 mm).
orrhage could penetrate the tumor and result in extratumoral Two patients underwent emergency surgery because of progres-
hemorrhage (Figure 2). On MRI with gadolinium enhancement, sive neurologic deficits and altered consciousness, and early surgery
the mass with a dural base showed moderate to strong was performed in the other 4 patients after the necessary preop-
enhancement except for the portion representing hemorrhage. erative evaluations. A macroscopically complete resection of the

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HONG-CAI WANG ET AL. UNDIFFERENTIATED MICROVESSELS IN MENINGIOMAS WITH INTRATUMORAL HEMORRHAGE

Table 1. Clinical Features of 6 Meningiomas with Intratumoral Hemorrhage


Age Tumor Tumor Tumor Resection
Case (Years) Sex Symptoms Location Hemorrhagic Type Subtype Size (mm) Grade Outcome

1 39 F Headache Parafalx Combined intra/extratumoral Fibrous 31 Simpson grade I Alive/no tumor


hemorrhage recurrence
2 45 M Headache Parasagittal Solitary intratumoral Atypical 39 Simpson grade II Alive/tumor
hemorrhage recurrence
3 51 F Headache/hemidysesthesia Convexity Combined intra/extratumoral Transitional 52 Simpson grade I Alive/no tumor
hemorrhage recurrence
4 53 F Headache/ Convexity Combined intra/extratumoral Angioblastic 47 Simpson grade I Alive/no tumor recurrence
hemiparesis hemorrhage
5 59 F Headache/ Convexity Solitary intratumoral Atypical 65 Simpson grade I Alive/hemiparesis/no
Hemiparesis/semicoma hemorrhage tumor recurrence
6 64 M Headache/ Parasagittal Combined intra/extratumoral Fibrous 41 Simpson grade II Alive/no tumor
hemiparesis hemorrhage recurrence

tumor and hematoma evacuation were performed in 1 stage for all These operative results were consistent with their corresponding
patients. During the operation, a solid extraparenchymal tumor and neuroimaging presentations (Figure 2). In all 6 patients,
intratumoral hemorrhage were found in all 6 patients; the surface of postoperative recovery was uneventful, and all patients were alive
the brain contacting the tumor was intact and not invaded by the at the time of this report; however, in 1 patient (patient 2), the
tumor. Two patients had intratumoral hemorrhage only, 1 patient tumor recurred within the 2-year follow-up period.
had intratumoral hemorrhage surrounded by intracerebral hemor- The diagnosis of meningioma was established according to
rhage, and the remaining 3 patients had intratumoral hemorrhage standard histopathological criteria following the World Health
along with subdural hematoma and subarachnoid hemorrhage. Organization system; these tumors were subtyped as transitional

Figure 2. Neuroimaging and intraoperative findings for representative case bleeding involving intratumoral hemorrhage, peritumoral hematoma,
4 with combined intratumoral/extratumoral hemorrhage. Preoperative CT subarachnoid hemorrhage, and subdural hemorrhage. The neuroimaging
scan (AeC) and MRI (EeG) showing an extrabrain mass lesion in the left presentations were demonstrated by operative results (D and H).
frontoparietal area, which displaced the adjacent brain and had acute

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HONG-CAI WANG ET AL. UNDIFFERENTIATED MICROVESSELS IN MENINGIOMAS WITH INTRATUMORAL HEMORRHAGE

Figure 3. Radiologic findings for representative case 2 with solitary no abnormal vessels such as aneurysms or vascular anomalies in the
intratumoral hemorrhage. Preoperative CT (AeD) and MRI (EeH) showing examination of CTA (BeD) and the superior sagittal sinus was partial
an extrabrain mass lesion in the right parietal parasagital area, which had stenosis in magnetic resonance venography (H).
acute intratumoral bleeding and partial moderate enhancement. There was

(n ¼ 1), angioblastic (n ¼ 1), fibrous (n ¼ 2), or atypical (n ¼ 2). are also 2 distinct types of blood vessels in meningiomas: undif-
As a control group, 12 patients with nonhemorrhagic meningi- ferentiated (CD31þ/CD34) and differentiated (CD31þ/CD34þ). By
omas were matched by sex, histological subtype, and lesion staining for the marker of SMA,14,17 we further assessed the pericyte
location; there were no significant differences in age or lesion size coverage of different tumor vessels. The corresponding results
between the patients with hemorrhagic meningiomas and controls showed that differentiated vessels were frequently surrounded by
(P < 0.05) (Table 2). Although there was no statistical analysis in pericytes, whereas undifferentiated vessels had few surrounding
this study, thin-walled dilated vessels, venous obstruction, and pericytes (Figure 5C and F). In summary, the morphologic
tumor infarction were observed more frequently on microscopic characteristics of undifferentiated vessels included absent or small
examination in the patients hemorrhagic meningiomas (Figure 4). lumen, no or less pericyte coverage, a thinner vessel wall, and
smaller size compared with the differentiated vessels.
Two Distinct Types of Blood Vessels
Of all the vasculature in meningiomas revealed by anti-CD31 anti- Correlation Between Tumor Vessels and Intratumoral Hemorrhage
body staining, most vessels could be stained by anti-CD34 antibody The vascular density of differentiated vessels was determined as
as well; however, certain blood vessels were stained only by anti- the CD34þ vessel count, and the number of undifferentiated
CD31 (Figure 5A, B, D, and E). According to previous studies on vessels was obtained by subtracting the CD34þ vessel count from
vascular differentiation and maturation, CD31 is expressed in both the CD31þ vessel count. The mean number of differentiated
differentiated and undifferentiated endothelial cells, and CD34 is vessels in hemorrhagic meningiomas was 49.7  12.1, compared
expressed only in differentiated endothelial cells.13-16 Thus, there with 54.2  14.6 in controls, a nonestatistically significant
difference (P > 0.05) (Figure 6). In addition, there was also
no significant difference in the mean number of CD31þ
Table 2. Differences in Age and Lesion Size Between the 2 vessels between the 2 groups (P > 0.05). However, the mean
Study Groups number of undifferentiated vessels was significantly higher in
hemorrhagic meningiomas than in controls (15.3  4.9 vs.
Hemorrhagic Control 6.4  3.6; P < 0.01).
Group (n [ 6) Group (n [ 12) t Statistic P Value

Age (years) 51.8  9.1 55.3  11.6 0.6433 >0.05 DISCUSSION


Tumor size (mm) 45.8  11.8 51.2  16.1 0.7253 >0.05 Meningiomas are most often slow-growing intracranial tumors
and usually present with symptoms such as headache, dizziness,

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Figure 4. Photomicrographs of surgical specimen. (A and B) Hematoxylin and eosinestained section of case 1 revealing
conventional meningioma of fibrous type with areas of hemorrhage, prominent congested vessels, thin-walled dilated
vessels, and extensive tumor infarction. (C and D) These pathological changes were not found in a control patient with
the same pathological subtype. (Original magnification, 200; scale bar: 100 mm.)

seizures, and gradually progressing neurologic deficits; however, Based on some clinical observations and pathological studies,
the clinical presentation of spontaneous hemorrhage is rare in the proposed mechanisms of hemorrhage in meningiomas could
these tumors.2,3,18 Although rare, major intracranial hemorrhage include rupture from weakened or unusual blood vessels, endo-
of meningiomas could have a dramatic effect on outcomes and thelial proliferation and subsequent vascular occlusion, direct
may even be a life-threatening event owing to acute increased vascular invasion by tumor cells, accumulation of bioactive sub-
intracranial pressure.2 The pathophysiological mechanism stances in meningiomas, concomitant vascular malformation or
underlying the bleeding remains unclear, however.3,18 Given its aneurysm, stretching and rupture of subdural bridging veins,
significant impact on patient outcomes especially for those with tumor growtheinduced venous compression associated with
acute onset of coma and its incomplete pathological character- peritumoral edema, and infarction owing to rapid growth of the
ization, a more in-depth understanding of the underlying patho- meningioma.2-11,18,22 Other factors that may increase the pro-
logical mechanism is needed. pensity of meningiomas to bleed involve hypertension, traumatic
Bleeding in a malignant tumor generally results from weakness head injury, irradiation, embolization of meningioma, and the use
of the neoplastic vessels, infiltration of tumor cells into the vessel, of anticoagulant medications.2,18,23-25 In addition, blood vessels at
and tendency of the mural endothelium to proliferate, which lead the interface between the meningioma and brain parenchyma also
to vessel destruction and necrosis.2-4,19 The mechanisms associ- have been suggested to play an important role in spontaneous
ated with spontaneous hemorrhage from nonmalignant menin- hemorrhage.26,27
giomas apparently are not exactly the same, however. There are a Along with histological type and tumor location, the mechanism
paucity of clinical trials on which to base decisions with regard to of hemorrhage in meningiomas also may vary according to the type
this agent, and some large studies on meningiomas have even of hemorrhage.2,18 Meningioma hemorrhage can present with
shown that none of the cases presented with clinically significant various bleeding patterns; some bleed only intratumorally, some
hemorrhage.20,21 Fortunately, some sporadic cases of spontaneous bleed only extratumorally, and some manifest both intratumoral
hemorrhage in meningiomas have been reported, and a combi- and extratumoral bleeding. Any one of the aforementioned theories
nation of several pathogenetic mechanisms has also been alone cannot totally explain the various hemorrhagic patterns seen
hypothesized to explain this rare condition over the past 3 occurring in meningiomas. For example, stretching and rupture of
decades.2-8,18,22 subdural bridging veins may explain only the extratumoral

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HONG-CAI WANG ET AL. UNDIFFERENTIATED MICROVESSELS IN MENINGIOMAS WITH INTRATUMORAL HEMORRHAGE

Figure 5. Histopathological findings for case 4 (AeC) and a control patient were stained only by CD31 (B and E). Staining for the marker of SMA
(DeF). Sections stained by CD31 revealed the highly vascularized tumors showed that those vessels revealed by CD34 were frequently surrounded
(A and D). Among all of the vasculature in meningiomas revealed by CD31 by pericytes, whereas some vessels only revealed by CD31 had few
staining, most vessels could be stained by CD34, but certain blood vessels surrounding pericytes. (Original magnification, 200; scale bar: 100 mm.)

hemorrhage involving subdural hematoma and subarachnoid In this study, we identified 6 patients with meningiomas with
hemorrhage. Rupture from weakened or unusual blood vessels is acute onset due to intratumoral hemorrhage and characterized
usually associated with intratumoral hemorrhage; in cases with them to explore the possible mechanism of such a bleeding
pure intratumoral hemorrhage, traumatic head injury is unlikely to pattern. Correspondingly, 2 distinct types of tumor vasculature
be a causative factor. However, few studies have explored the of undifferentiated (CD31þ/CD34) and differentiated (CD31þ/
mechanisms relevant to the specific pathoanatomic types of hem- CD34þ) vessels were first determined in meningiomas. Most
orrhage, and inconsistent results have been derived from reports of importantly, only the mean number of undifferentiated vessels
unclassified hemorrhage patterns. Some authors have suggested was significantly higher in hemorrhagic meningiomas than in
that intratumoral vasculature may be the most logical explanation controls (15.3  4.9 vs. 6.4  3.6; P < 0.01). Neither differen-
for this condition and have emphasized a high risk of hemorrhage tiated vessels nor the total number of blood vessels showed
in angioblastic and malignant meningiomas.4,8,18,24 In contrast, a significant difference between the 2 groups (P > 0.05). It
other authors did not identify any relationship between intratumoral also should be noted that the mild discrepancy of tumor
vasculature and elevated risk of hemorrhage.3,9,11 vascularity counted by CD34 staining vs. CD31 staining could
The apparent discrepancy also may be explained in part by the result from a systemic error in different sections for the 2
fact that different studies applied various or multiple blood vessel separate staining processes; for example, a specific vessel in a
markers. Blood vessel markers used to identify tumor blood ves- tissue section could disappear or become 2 separate vessels in
sels are diverse and heterogeneous, and could reveal different the next section.13 In addition, the technique for identifying
aspects and characteristics of the tumor vasculature.13,14 Different hotspots in a tumor was subject to the interobserver and
features of blood vessels have been identified in prostate cancer, intraobserver variability.
lung cancer, and renal cell carcinomas through various vascular To further explore the characteristics of tumor vessels, the
markers.12-14 It also has been reported that CD34 is expressed only pericyte coverage of blood vessels was evaluated by staining for the
in differentiated endothelial cells, whereas CD31 is a panvascular pericyte marker SMA. The results demonstrated that undifferen-
marker commonly found in the vessel system and expressed in tiated vessels had few surrounding pericytes and were more apt to
both differentiated and undifferentiated endothelial cells.28 For rupture. In addition, thin-walled dilated vessels, venous obstruc-
example, 2 distinct types of blood vessels have been identified tion, and tumor infarction were also common in hemorrhagic
in renal cell carcinoma: undifferentiated vessels (CD31þ/CD34) meningiomas. Based on these observations, the tumor vasculature
and differentiated vessels (CD31þ/CD34þ). Only undifferentiated in meningiomas is heterogeneous, and undifferentiated vessels
vessels had a significant correlation with higher tumor grades.14 may play a pivotal role in the spontaneous intratumoral bleeding

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ORIGINAL ARTICLE
HONG-CAI WANG ET AL. UNDIFFERENTIATED MICROVESSELS IN MENINGIOMAS WITH INTRATUMORAL HEMORRHAGE

without surgery are at definite risk for intratumoral hemorrhage.


The time interval from initial presentation to hemorrhage has not
been explored, however.
Although the relationship between undifferentiated vessels and
intratumoral hemorrhage is demonstrated in the present study,
this finding is still preliminary and limited by the small number of
these cases. Future research will focus on such issues as a larger
number of cases to confirm our findings, the interval from initial
presentation to tumor bleeding, the characterization of tumor
vasculature in meningiomas with pure extratumoral hemorrhage,
and the differences in pathological changes between the 2 hem-
orrhagic types.

CONCLUSION
The tumoral vasculature in meningiomas is heterogeneous, and 2
distinct types of blood vessels involving differentiated and undif-
ferentiated vessels were first determined in our study. Undiffer-
entiated blood vessels cannot alone reliably account for all the
intratumoral hemorrhage in meningiomas, but that seem to
Figure 6. Bar graph showing the difference in mean number of tumor
vessels between patients with hemorrhagic meningioma and controls. contribute to a fragile state of tumor vasculature that can be dis-
There was no significant between-group difference in the mean number rupted by a precipitating event, thus leading to spontaneous
of total tumor vessels (P > 0.05). The difference in mean number of hemorrhage.
differentiated vessels between the 2 groups also was not statistically
significant (P > 0.05); however, the mean number of undifferentiated
vessels was significantly different between patients with hemorrhagic
meningioma and controls (P < 0.01). Data are presented as mean  ACKNOWLEDGMENTS
standard deviation, and error bars represent standard deviation. We thank our patients and their guardians for giving us permis-
sion to publish these cases with the pictures. This work is sup-
of meningiomas. The results also suggest that certain patients ported by grants from the Ningbo Social Development Research
with meningiomas who are being maintained on follow-up Project (2013A05 and 2014C50089).

haemorrhage. Acta Neurochir (Wien). 2000;142: for IBeIIA non-small cell lung cancer. J Clin Pathol.
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ORIGINAL ARTICLE
HONG-CAI WANG ET AL. UNDIFFERENTIATED MICROVESSELS IN MENINGIOMAS WITH INTRATUMORAL HEMORRHAGE

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