ARTICLE
Auteur(s) : Yuguang
Liu, Meng Liu, Feng Li, Chengyuan Wu, Shugan Zhu
Department of Neurosurgery, Qilu Hospital of Shandong
University, Jinan, 250012, P.R. China
Meningiomas have been described as a kind of benign tumor for
nearly 200 years, but the existence of malignant meningioma (MM)
wasn’t clearly recognized until 1938 [1]. MM means the kind of
meningioma featuring malignant brain tumours such as rapid growth,
brain invasion, easy recurrence and metastasis as well as the
general manifestations of benign meningioma (BM), which is a
clinicopathological entity [2, 3]. It was reported that the ratio
of MMs to intracranial meningiomas varied greatly from 0.9 to 20%,
with an average of 2.8% in the literature because of a lack of
universally accepted diagnostic criteria [2-6]. The objective of
this retrospective study was to assess clinical features,
management and the presence of variables that predict outcome in
patients with MM.
Clinical materials and methods
According to WHO classification criteria of meningioma [2], 22
patients with MM were surgically treated between January 1986 and
January 2005 in Qilu hospital, and confirmed by postoperative
pathohistological examination. Patient charts, including surgical
records, discharge letters, histological reports, follow-up
records, and imaging studies, were meticulously analyzed
retrospectively. Collected data were studied with the focus on the
patient’s age and sex, tumor site of origin, duration of first
presenting symptom, neurological deficits, neuroimaging appearance,
surgical management, and outcome as well as clinical and
neuroimaging follow-up findings.
Before surgery, all patients received a Karnofsky performance
scale (KPS) rating, and underwent a general neurological
examination and neuroimaging examinations (CT or MR imaging). CT or
MR imaging was acquired within 72 hours postoperatively, and the
same imaging protocol was used during follow-up. The patients’ KPS
scores were assessed again at approximately 1 weeks and 12 months
postsurgically.
Statistical analyses
Survival time was measured in months from the date of the patient’s
first craniotomy to the date of death or the date of the last
follow-up evaluation for patients who were still alive. The
differences between the pre- and postoperative KPS scores were
tested using a paired t-test. Patient survival and recurrence-free
survival was calculated using the nonparametric Kaplan-Meier
method. Univariate analysis was performed with tests of significant
differences between Kaplan-Meier curves based on the log-rank
statistic, and multivariate analysis was performed with the Cox
proportional hazards method. Statistical significance was defined
as a probability value less than 0.05, and statistical calculations
were performed using standard statistical processing software
(SPSS, version 13.0).
Results
Demographic data
There were 12 males and 10 females, and age ranged from 32 to 70
years (mean 52.5) in this series. Subacute onset occurred in 2
cases and chronic onset in 20. The duration of symptoms from onset
to diagnosis was between 20 days and 112 days (mean 56 days). The
follow-up period ranged from 6 months to 10 years.
Symptoms and signs
The symptoms and signs of 22 patients with MM are listed in table
1( Table 1 ).
Table 1 The symptoms and signs of 22 patients with MM
|
Symptoms
|
No.
|
%
|
Signs
|
No.
|
%
|
|
Headache
|
16
|
72.7
|
Unilateral facial palsy
|
1
|
4.5
|
|
Nausea, vomiting
|
16
|
72.7
|
Unilateral vision decrease
|
2
|
9.1
|
|
Convulsion
|
4
|
18.2
|
Bilateral papilledema
|
12
|
54.5
|
|
Memory decrease
|
5
|
22.7
|
Mild hemiplegia
|
9
|
40.9
|
|
Character change
|
4
|
18.2
|
Partial aphasia
|
3
|
13.6
|
|
Diplopia
|
3
|
13.6
|
No signs
|
2
|
9.1
|
Radiological manifestations
Non-enhancement and enhancement CT scanning were performed in all
patients and MRI examination in 16 cases. The radiological
manifestations of 22 patients with MM are listed in table 2( Table 2 ).
Table 2 The radiological manifestations of 22 patients
with MM
|
Radiological manifestations
|
No.
|
%
|
|
Tumor diameter (cm)
|
|
|
|
≤ 3
|
1
|
4.5
|
|
3~5
|
8
|
36.4
|
|
5~7
|
10
|
45.5
|
|
≥ 7
|
3
|
13.6
|
|
Tumor location
|
|
|
|
Convexity
|
7
|
31.8
|
|
Left
|
3
|
13.6
|
|
Right
|
8
|
36.4
|
|
Parasagittal
|
4
|
18.2
|
|
Sphenoid ridge
|
|
|
|
Tumor density
|
|
|
|
Hyper
|
8
|
36.4
|
|
Iso
|
9
|
40.9
|
|
Mixed
|
5
|
22.7
|
|
Tumor enhancement
|
|
|
|
Homogeneous
|
8
|
36.4
|
|
Nonhomogeneous
|
14
|
63.6
|
|
Tumor boundary
|
|
|
|
Clear
|
6
|
27.3
|
|
Obscure
|
16
|
72.7
|
|
Tumor shape
|
|
|
|
Mushroom
|
15
|
68.2
|
|
Sublobe
|
4
|
18.2
|
|
Flat
|
3
|
13.6
|
|
Peritumor edema
|
|
|
|
Marked
|
22
|
100.0
|
|
Midline shift
|
|
|
|
No
|
4
|
18.2
|
|
Yes
|
18
|
81.8
|
Surgical technique
Surgical resection and adjuvant radiotherapy were performed in all
patients. According to Simpson grade criteria [7], grade I
resection was achieved in 16 cases, and grade II in 6. Second
surgical removal was performed in 12 cases after recurrent tumors
were detected. Intraoperatively, it was found that infiltrative
growth, marked peritumoral edema and obscure margin were the main
characteristics, as well as blood vessels communicated with brain
tissue in most cases. The tumor was easy to remove because of its
fragile texture, poor blood supply and frequent partial necrosis,
which were quite different from the BM.
Pathological features
Brain invasion accompanied by marked cerebral edema were present in
all cases, and loss of architecture, nuclear pleiomorphism and
obvious mitoses in 18 cases. In addition, it was found there
were multiple small necrotic areas in the center of tumor with
increased mitosis.
Complications and prognosis
No perioperative death occurred in this series. After operation,
the temporary aggravation of hemiplegia or aphasia occurred in
12 cases, which disappeared or improved 3 months after
operation (median 1.7 months). In all patients improved KPS scores
were observed at 12 months postoperatively compared with the
preoperative scores, and this improvement was statistically
significant (p = 0.0001) (figure 1).
The overall survival and recurrence-free survival were shown for
all 22 patients in figure 2. The median
survival time was 38 months, and overall survival rates at
6 months and at 1, 3, 5, and 10 years postoperatively were
100, 77.3, 50, 36.4, and 22.7%, respectively. The median
recurrence-free survival time was 31.4 months, with 81.8, 63.6,
36.4, 27.3, and 13.6% of patients alive without recurrence at 6
months and at 1, 3, 5 and 10 years post surgery, respectively. As
shown in (figures 3
and 4), median duration of both survival and
recurrence-free survival of 16 patients with Simpson Grade I
resection was significantly longer than that of 6 cases with
Simpson grade II resection (70 versus 10 months, p = 0.0001; and
50.3 versus 5 months, p = 0.0001). Recurrent meningiomas were
diagnosed in 19 patients, and their median survival time was
35 months. The median interval from the initial craniotomy to
diagnosis of recurrence was 23.4 months (range 3-119 months). In 12
of these patients the recurrent tumor was resected (figure 5), and this
subgroup survived significantly longer than the 7 patients who did
not undergo a second craniotomy (median survival time 40 months
compared with 11 months, respectively; p = 0.005). One case with
Simpson grade II resection died of recurrence of tumor and
pulmonary metastasis 14 months after operation.
In the Cox multivariate analysis, 5 variables were analyzed
(patient age, sex, tumor location, tumor size, and location). Only
Simpson grade II resection and location of the tumor in the
non-convexity had an adverse impact on survival (table 3)( Table 3 ).
Table 3 Multivariate analysis of factors influencing
survival times
|
Factors
|
B
|
SE
|
P value
|
RR
|
|
Age
|
0.027
|
0.035
|
0.444
|
1.027
|
|
Sex
|
0.861
|
0.672
|
0.201
|
2.365
|
|
Location
|
1.719
|
0.715
|
0.016
|
5.580
|
|
Size
|
-0.179
|
0.268
|
0.506
|
0.836
|
|
Surgery
|
2.169
|
0.708
|
0.002
|
8.753
|
Discussion
Diagnostic criteria
The diagnosis of MM was established by combination of clinical
manifestations and pathohistological features. Sometimes, the
discrimination of benign meningioma (BM) from MM was difficult [8].
Clinically, if the meningioma manifests as malignant behaviors such
as rapid growth in a short time, extracranial metastasis, or
aggressiveness and implantation in subarachnoid space, it can be
diagnosed as MM [2, 4, 6, 8]. Both recurrent BM and atypical
meningioma can turn into MM [2, 8]. According to the meningioma
classification of WHO 2004, malignant meningiomas (WHO grade III)
have a mitotic rate of 20 or more mitoses per 10 high-power fields
or exhibit histologic features of frank malignancy that resemble
carcinoma, sarcoma, or melanoma.
Clinical characteristics
MM is characterized by the following: 1) the age of MM is much
younger than that of BM; 2) the course of the illness is shorter;
3) 38.5 ~ 57% of MMs come from recurrent BMs [6]; 4) MMs are
mainly located in the convexity, parasagittal sinus and sphenoid
ridge; 5) patients with MM usually have lower incidence rates of
convulsion, motional and sensory disturbance and other nervous
system lesions than those with BM [2, 3]; 6) extracranial
metastases may occur in lung, bone marrow, muscle, vertebral body,
liver or lymph nodes though they are uncommon, and sometimes,
implantation in subarachnoid space occurs [3, 9, 10]. In our
series, only one patient had pulmonary metastasis during follow-up.
Radiological manifestations
Though MM lacks special radiological manifestations, the risk that
the meningioma is malignant will be much higher if the tumor
displays the following radiological features [2, 8, 11-13]: 1)
marked peritumoral edema without calcification; 2) no rat-tail
sign; 3) mushroom, sublobe or flat shape with irregular or obscure
border; 4) nonhomogeneous enhancement; 5) focal necrosis in the
center of tumor; 6) arteriovenous shunt indicated by cerebral
angiography. Vassilouthis et al. considered that the meningioma was
probably malignant if the tumor had the following CT features such
as marked surrounding edema combined with an absence of visible
calcification, or presence of cystic components in nonhomogeneous
contrast enhancement with irregular border [11].
Pathological features
Pathohistological features of MM include high mitotic count,
hypercellularity, loss of architecture, nuclear pleiomorphism,
focal necrosis, brain infiltration or metastasis [2, 4, 8, 10, 14,
15]. The mitotic count of tumor cells stand for the active degree
of cells growth, and the atypical mitosis is one of markers of MM
[15]. However, it is sometimes difficult to attain reliable results
because the distribution of meningioma mitosis is highly variable
[16]. With the increasing malignancy of meningioma, its inherent
architecture is lost, which shows loss of regular arrangement of
cells, flaky or zonal neoplastic cells, and homogeneous ovate
nucleus with rich nucleoli [8, 10]. It trends to be malignant if
the tumors contain hemosiderin pigmentation and exoderma component
of blood vessel associated with marked peritumoral edema [8,
15].The infiltration of meningioma into the surrounding tissue or
extracranial metastasis is also the sign of malignancy [5].
Treatment and prognosis
Surgical excision and adjuvant radiotherapy are the main procedures
for MM. The biological characteristics of MM determine its poor
prognosis. The average survival of MM with total removal is in the
order of 2 years, and could be extended as long as 5 years if
postoperative radiotherapy was performed [13]. It is reported that
the postoperative 3-year and 5-year recurrence rate of MM range
from 33 to 80% and from 75 to 85% respectively [2, 5, 17], the
5-year survival rate of total resection and subtotal resection was
39 and 0% respectively, and the 5-year survival rate was 48% if
radiotherapy was administered after subtotal excision of MM [2, 6].
However, Palma et al. reported 5-year and 10-year survival rates of
MM after surgery as high as 64.3 and 34.5% [6]. We consider Simpson
grade II resection as non-total in consideration of the
infiltrative growth of MM. In this group, 3-year, 5-year and
10-year recurrence rates of patients with Simpson grade I resection
and adjuvant radiotherapy were 50, 62.5 and 81.3% respectively, and
the 1-year recurrence rate of patients with Simpson grade II
resection and adjuvant radiotherapy was 100%. Similarly, 3-year,
5-year and 10-year survival rates of patients with Simpson grade I
resection and adjuvant radiotherapy were 62.5, 50 and 31.3%
respectively, and the 5-year survival rate of patients with Simpson
grade II resection and adjuvant radiotherapy was 0%. From these
results, we can conclude that the degree of tumoral removal is the
main factor determining recurrence and survival of patients with
MM. Dziuk et al. reported that the 5-year survival rate of simple
total resection was 28%, and increased to 57% in case of total
resection with adjuvant radiotherapy [6]. They thought the degree
of resection was the crucial factor influencing postoperative
survival duration, but the total resection could not prevent
recurrence of tumor, while the adjuvant radiotherapy could prolong
survival time [6].
Conclusion
In conclusion, malignant (anaplastic) meningioma constitutes a rare
subset of meningioma. It displays infiltrative growth and
postoperative recurrence even if tumor total excision and
radiotherapy are performed. Surgical resection and adjuvant
radiotherapy are the main treatments for MM, and the degree of
tumor removal is the main factor determining postoperative
recurrence and survival.
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