Keywords:
Brain Neoplasms - Epidemiology - Prevalence
Palavras-chave:
Neoplasias Encefálicas - Epidemiologia - Prevalência
INTRODUCTION
Disordered proliferation of brain cells originates tumors, which may be malignant
or non-malignant[1],[2],[3]. In Brazil, it has been estimated that 11,090 new cases of malignant central nervous
system (CNS) tumors will occur in 2020. Except for non-melanoma skin cancer, CNS neoplasms
correspond to the tenth most prevalent type of cancer among women in Brazil, and are
the ninth most frequent among men and women in the northeastern region of Brazil[4]. Because of the location, unpleasant neurological deterioration may be seen in cases
of both malignant and non-malignant CNS tumors. Moreover, these neoplasms are responsible
for significant mortality in the population[4],[5],[6],[7].
The World Health Organization (WHO) published a new update on the classification of
tumors of the central nervous system in 2016. In this, their classification came to
incorporate molecular characteristics, in addition to the histological aspects of
tumor entities. The new perspective has an impact on diagnosing tumor types since
it enhances discrimination between subtypes resembling histopathological categories
and therefore optimizes the accuracy of diagnosis[8],[9],[10].
Because of the heterogeneity of these tumors and the different methods used in studies,
their precise epidemiological description is complex[11],[12],[13]. Moreover, many sites do not have a non-malignant tumor registration system. This
limits the analysis on the distribution and characterization of these entities in
the population[14].
Comparative studies have shown increasing incidence of CNS tumors over the years[15],[16],[17]. This may be occurring through increased exposure to possible risk factors such
as high-dose irradiation or genetic syndromes, or through improved access to screening
imaging tests[18],[19],[20]. Furthermore, it has been suggested in some studies that the increasing use of wireless
devices and cordless phones are risk factors for the development of CNS tumors[21],[22].
In Sergipe, a state in northeastern Brazil, few studies have evaluated the epidemiology
of CNS tumors. This state does not have a notification system for benign CNS tumors,
which highlights the importance of epidemiological studies based on the histopathological
diagnosis of these entities. In Aracaju, a city located in Sergipe, the population-based
cancer registry (RCBP) possesses a high-quality database, that supports national ratings
for the incidence of primary malignant CNS tumors. This formed a reference point for
parallels with the findings of the present study.
The objective of this study was to characterize the CNS primary tumors in Sergipe
between 2010 and 2018. Through these data, we described the current panorama of distribution
of these entities, with the aim of contributing to knowledge of the epidemiology of
these tumors.
METHODS
Study design
This was an observational and descriptive retrospective longitudinal study in which
histopathological reports on patients who underwent removal of primary CNS tumors
in the state of Sergipe, Brazil between January 2010 and December 2018 were analyzed.
The reports were collected from the database laboratories in Sergipe that agreed to
participate in the study.
Inclusion criteria
All patients who underwent surgery to treat primary CNS tumors in the state of Sergipe,
between January 2010 and December 2018, and whose histopathological material was analyzed,
were included in this study. Patients were enrolled regardless of their place of residence
since their addresses were not available from the laboratories that attended to these
cases.
Exclusion criteria
We excluded patients whose histopathological reports were inconclusive, along with
cases of metastasis. Among the histopathological reports, 52 cases were found to be
inconclusive or contained incomplete information, and were therefore excluded from
this study.
Data collection technique and instruments
The data-gathering period was between November 2018 and February 2019. After the methodology
of the current project had been presented to the Research Ethics Committee of the
Federal University of Sergipe and approval had been granted, data collection at the
laboratories that agreed to participate started.
Five anatomopathological laboratories located in Aracaju, Sergipe, are registered
in the National Register of Healthcare Establishments (CNES). Four out of these five
were responsible for all of the anatomopathological reports on brain surgeries in
Sergipe, and all of them agreed to participate in this current research.
The data analysis followed the 2016 WHO classification for stratification of CNS tumors,
in which the tumors are divided into four groups, according to increasing degrees
of severity, ranging from grade I to IV. In 2016, an updated classification was published,
incorporating molecular characteristics to define tumor entities[10]. We used this updated classification for CNS tumors, but no molecular analysis had
been performed in most cases. Therefore, given the small number of cases with molecular
analysis, it was decided not to describe molecular data in this current study. After
data collection, we analyzed the prevalence of tumors and their epidemiological characteristics
according to the variables of age, sex and location, in accordance with the categories
of the International Classification of Diseases, 10th edition (ICD-10), WHO grade and histological tumor type.
Ethical considerations
This study was approved by the Research Ethics Committee of the Health Campus of the
Federal University of Sergipe (UFS). No consent form was applied because no personal
identification of the patients was used. Nor was there any analysis of medical records
or contact with any patient. Confidentiality of information regarding healthcare service
user identification and anonymity in future publication of results will remain assured.
Statistical data analysis
The data were systematized, analyzed and statistically tested using the Statistical
Package for the Social Sciences (SPSS) software version 20.0 and the R software version
3.5.0. The variables were described through absolute and relative frequencies, medians,
arithmetic means and standard deviations. After descriptive analysis, it was investigated
whether the data followed normal distribution of probability, using the Kolmogorov-Smirnov
test. The results of interest were tested using the nonparametric Mann-Whitney test.
RESULTS
Epidemiology of primary CNS tumors in the state of Sergipe between 2010 and 2018
Altogether, 861 primary CNS tumors were found in Sergipe between 2010 and 2018, after
applying the study exclusion criteria. Out of the total, 56.9% (n=490) were in females
and 43.1% (n=371) were in males. Overall, neuroepithelial tumors accounted for 50.2%
(n=433) of the cases. Gliomas occurred most frequently, comprising 64.2% (n=278) of
these entities and 32.3% (n=278) of the entire sample. Glioblastoma was the most common
type of glioma, corresponding to 63.7% (n=177) of the glioma cases. Meningiomas were
the second most prevalent tumor, present in 29.6% (n=255) of the sample. The meningothelial
and transitional histological types of meningiomas accounted for 40.3% (n=103) and
25.4% (n=65) of the cases, respectively ([Table 1]). Meningiomas were the most common tumors in females, whereas among males, gliomas
occurred most frequently ([Table 1]).
Table 1
Distribution of primary central nervous system tumors according to histological groups,
Sergipe, Brazil, 2010–2018.
|
Histological groups
|
Males
|
Females
|
Total
|
|
n
|
%
|
n
|
%
|
n
|
%
|
|
Gliomas
|
144
|
51.8
|
134
|
48.2
|
278
|
32.3
|
|
Meningiomas
|
73
|
28.6
|
182
|
71.3
|
255
|
29.6
|
|
Medulloblastomas
|
31
|
51.7
|
29
|
48.3
|
60
|
7.0
|
|
Ependymal tumors
|
21
|
50.0
|
21
|
50.0
|
42
|
4.9
|
|
Other astrocytic tumors
|
24
|
48.9
|
25
|
51.0
|
49
|
5.7
|
|
Schwannomas and neurofibromas
|
45
|
52.9
|
40
|
47.1
|
85
|
9.9
|
|
Tumors of the pineal region
|
2
|
50.0
|
2
|
50.0
|
4
|
0.5
|
|
Hemangiomas and hemangioblastomas
|
8
|
44.4
|
10
|
55.6
|
18
|
2.1
|
|
Craniopharyngiomas
|
2
|
33.4
|
4
|
66.6
|
6
|
0.7
|
|
Pituitary adenomas
|
14
|
31.8
|
30
|
68.2
|
44
|
5.1
|
|
Neuronal and mixed neuronal-glial gliomas
|
6
|
31.6
|
13
|
68.4
|
19
|
2.2
|
|
Germ cell tumors
|
2
|
100
|
-
|
-
|
2
|
0.2
|
The histological groups were also evaluated according to age groups. In the population
from 0 to 14 years of age, 98 tumors were found. The group of "other astrocytic tumors"
was the most prevalent, comprising 29.6% (n=29) of these entities. This group was
followed by medulloblastomas and ependymal tumors, with 27.6% (n=27) and 14.3% (n=14)
of the cases for this age group, respectively ([Table 2]).
Table 2
Distribution of primary central nervous system tumors according to histological group
and age range, Sergipe, Brazil, 2010-2018.
|
Age group
|
Histological groups % (n)
|
|
Gliomas
|
Meningiomas
|
Medulloblastomas
|
Ependymal tumors
|
Other astrocytic tumors
|
Pituitary tumors
|
|
0–14
|
5.4% (15)
|
-
|
45.5% (30)
|
37.5% (15)
|
61.2% (30)
|
-
|
|
15–19
|
4.7% (13)
|
1.17% (3)
|
1.5% (1)
|
7.5% (3)
|
4.1% (2)
|
2.2% (1)
|
|
20–44
|
25.9% (72)
|
22.3% (57)
|
37.9% (25)
|
42.5% (17)
|
32.7% (16)
|
51.1% (23)
|
|
45–54
|
21.9% (61)
|
31.0% (79)
|
9.1% (6)
|
12.5% (5)
|
2.0% (1)
|
17.8% (8)
|
|
55–74
|
35.9% (100)
|
34.5% (88)
|
6.1% (4)
|
-
|
-
|
26.7% (12)
|
|
>75
|
6.1% (17)
|
11% (28)
|
-
|
-
|
-
|
2.2% (1)
|
In the population between 15 and 34 years old, 165 cases were found, which represented
19.2% of the study population. Gliomas occurred most frequently, in 32.7% (n=54) of
the cases. In the 35 to 74 age group, which represented 50.4% (n=434) of the population,
meningiomas were the most common neoplasms, affecting 47.5% (n=206). The same trend
was observed in the sample aged 75 years or over, in which meningiomas were responsible
for 61.2% (n=30) of these cases ([Table 2]).
The locations of the tumors were stratified according to the ICD-10 classification.
The following locations were found: brain (C70.0, C71.0 to C71.4, C71.8, C71.9), brainstem
(C71.7), cerebellum (C71.6), ventricles (C71.5) spinal cord (C70.1, C72.0, C72.1),
pineal gland (C75.3, D35.4, D44.5), sella (C75.1, C75.2, D 35.2, D44.3) and unspecified
(C70.9, C72.9). Other locations were classified under codes C72.2 to C72.5. The brain
was the most common site, followed by the cerebellum ([Figure 1]). Among the gliomas and meningiomas, the brain was affected in 79.5% (n=221) and
70.6% (n=180) of the cases, respectively. Evaluation of sex and location in relation
to meningiomas showed a ratio of 2.4 women for each man, for spinal tumors. Among
cerebral tumors, a ratio of 2.3 women for each man with meningioma was found.
Figure 1 Distribution of primary central nervous system tumors according to the originating
site, Sergipe, Brazil, 2010–2018.
In the groups of medulloblastomas and other astrocytic tumors, the cerebellum was
the most frequent location, which corresponded to 43.3% (n=26) and 28.6% (n=14) of
the cases, respectively. For ependymal tumors, the intraventricular site was the most
affected, accounting for 26.2% (n=11) of these neoplasms. The sella site was the location
of 100% (n=44) of pituitary adenomas and 50% (n=3) of craniopharyngiomas. The pineal
gland was the site of 100% (n=2) of germ cell tumors.
Regarding the WHO grade, the largest proportion of the tumors were classified as grade
I, which represented 43.9% (n=378) of the cases, followed by grade IV tumors, corresponding
to 27.9% (n=240) of the sample. The entities classified as grade II and grade III
represented 14.1% (n=121 and 6% (n=52) of the cases, respectively ([Tables 3] and [4]).
Table 3
Distribution of primary central nervous system tumors according to histology and World
Health Organization grade in children (age 0–14 years), Sergipe, Brazil, 2010–2018.
|
Histological group
|
Grade I
|
Grade II
|
Grade III
|
Grade IV
|
Unspecified
|
|
n
|
%
|
n
|
%
|
n
|
%
|
n
|
%
|
n
|
%
|
|
Medulloblastomas
|
-
|
-
|
-
|
-
|
-
|
-
|
26
|
96.2
|
1
|
3.7
|
|
Gliomas
|
-
|
-
|
3
|
20.0
|
1
|
6.7
|
11
|
73.3
|
-
|
-
|
|
Other astrocytic tumors
|
29
|
100
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Ependymal tumors
|
-
|
-
|
11
|
78.5
|
3
|
21.4
|
-
|
-
|
-
|
-
|
|
Schwannomas and neurofibromas
|
3
|
100
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Neuronal and mixed neuronal-glial gliomas
|
6
|
85.7
|
-
|
-
|
-
|
-
|
-
|
-
|
1
|
14.3
|
|
Craniopharyngiomas
|
-
|
-
|
1
|
100
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Tumors of the pineal region
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
2
|
100
|
Table 4
Distribution of primary central nervous system tumors according to histology and World
Health Organization graduation in adolescents and adults (age ≥15 years), Sergipe,
Brazil, 2010–2018.
|
Histological group
|
Grade I
|
Grade II
|
Grade III
|
Grade IV
|
Unspecified
|
|
n
|
%
|
n
|
%
|
n
|
%
|
n
|
%
|
n
|
%
|
|
Gliomas
|
-
|
-
|
56
|
21.4
|
37
|
14.1
|
168
|
64.1
|
2
|
0.76
|
|
Meningiomas
|
218
|
85.8
|
29
|
11.4
|
5
|
1.96
|
-
|
-
|
3
|
1.17
|
|
Medulloblastomas
|
-
|
-
|
-
|
-
|
-
|
-
|
32
|
96.7
|
1
|
3.03
|
|
Other astrocytic tumors
|
17
|
85.0
|
1
|
5.0
|
-
|
-
|
-
|
-
|
2
|
10.0
|
|
Ependymal tumors
|
4
|
14.3
|
17
|
60.7
|
6
|
21.4
|
1
|
3.6
|
-
|
-
|
|
Schwannomas and neurofibromas
|
82
|
100
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Neuronal and mixed neuronal-glial gliomas
|
1
|
8.3
|
3
|
25.0
|
-
|
-
|
-
|
-
|
8
|
66.7
|
|
Craniopharyngiomas
|
5
|
100
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Tumors of the pineal region
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
2
|
100
|
|
Hemangioma and hemangioblastomas
|
13
|
72.2
|
-
|
-
|
-
|
-
|
-
|
-
|
5
|
27.8
|
|
Pituitary adenomas
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
44
|
100
|
|
Germ cell tumors
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
1
|
100
|
From the second decade of life onwards, increasing numbers of cases were observed.
Moreover, there was a peak between the fourth and sixth decades of life, with subsequent
reduction. From 2010 to 2018, the average number of tumors per year was 86.1 (±97.5).
DISCUSSION
The present study describes the epidemiological aspects of primary CNS tumors diagnosed
in Sergipe between 2010 and 2018. The patients’ ages ranged from 6 to 92 years, with
a mean of 44.6 years. Patients aged between 45 and 54 years predominated, representing
20.4% (n=176) of the cases. Regarding the epidemiological characterization, predominance
of female cases was observed, which corresponded to 56.7% of all the cases. Males
accounted for 43.1% of the sample. Although these data from 2010 to 2018 diverged
from findings over the previous decade in Sergipe[23], they were in line with results from other studies[24],[25]. In a previous study in which 2,131 primary CNS tumors were evaluated, 53.7% of
the sample was represented by females, while 46.2% were male patients[26]. Similar data were described in the Central Brain Tumor Registry of the United States
(CBTRUS). In that series, women comprised 57.9% of all cases of CNS tumors diagnosed
in the United States between 2010 and 2014, while men accounted for 42.1%[14].
In Aracaju, Sergipe, a population-based cancer registry (RCBP) collects high-quality
epidemiological data from this state. These data are taken to the National Cancer
Institute (INCA) to aggregate with the national estimates for cancer in Brazil. According
to INCA data, which are based on what is collected by each state’s RCBP, the estimate
for the number of new cases of primary malignant neoplasms of the CNS in Brazil, in
2020, was 11,090 cases. Out of this total, 5,870 were estimated to be among males
and 5,220 among females. In Sergipe, 90 new cases were expected in 2020: 40 in males
and 50 in females[4]. These estimates are compatible with the data obtained in the present study. However,
both benign and malignant tumors were evaluated, which can be explained by the fact
that a significant percentage of CNS tumors are not diagnosed through histopathology
in Sergipe[27].
Meningiomas were more prevalent in females than in males, with a ratio of 2.3:1, respectively.
This finding is consistent with data from previous studies, which reported that meningeal
tumors were approximately three times more frequent among females than among males[19],[25],[28].
Neuroepithelial tumors comprised approximately half of all the neoplasms observed
(50.2%). Among the different histological groups, gliomas had the highest prevalence
(32.3%) in the entire sample, followed by meningiomas (29.6%). These findings are
consistent with data from other studies in the current literature[26],[29].
Regarding age groups, a mean age at the time of diagnosis of 44.64 years was observed.
This was lower than what was found in another similar study[30]. The peak prevalence was observed between 45 and 54 years of age, with a subsequent
reduction in the number of tumors, especially after the sixth decade of life. These
findings are similar to those described in other studies[23],[31]. Higher prevalence of other astrocytic tumors in the age group of 0–14 years was
described in previous studies[12],[14]. Increasing numbers of meningioma cases in older age groups were also described
in other studies[14],[32].
A similar study conducted previously described the epidemiology of CNS tumors in the
state of Sergipe between the years 2000 and 2010[23]. In that study, 775 primary CNS tumors were found. Male sex was more prevalent,
corresponding to 50.8% (n=429) of the cases. Meningiomas and glioblastomas were the
predominant histological types, which represented 21% (n=177) and 18.7% (n=158) of
the cases, respectively[23].
There was an absolute increase in the number of tumors from the previous cohort to
the current one, although without statistical significance (p=0.762). We emphasize
that some bias exists in this comparison since we cannot confirm that the populations
compared were homogeneous or that the methods used in the previous study were similar
to those used in the present study. The growth in the number of CNS neoplasms that
we observed is a trend corroborated by other studies; however, the evidence is conflicting.
In a meta-analysis on 38 articles that was performed in 2014, there were no statistically
significant changes in CNS tumor incidence rates[33]. However, in a study based on the Girona cancer registry, an increase in the incidence
of CNS neoplasms between 1994 and 2013 was described, consisting of greater numbers
of non-malignant tumors[26]. This divergence can possibly be explained in terms of the great heterogeneity of
entities among CNS tumors. Moreover, the methodologies and classifications used to
study these neoplasms have differed between many of the studies conducted.
In the present study, a progressive increase in the number of tumors diagnosed was
found between 2010 and 2018. Other studies have sought to investigate risk factors
for possible increased incidence of these tumors[22],[34],[35],[36]. However, increased life expectancy, greater access to diagnostic tests for the
population and population growth may influence these findings[18].
The main limitation of the present study was the significant number of cases that
fulfilled the exclusion criteria. These cases were excluded because, in some databases,
it was not possible to access immunohistochemical reports to confirm inconclusive
histopathological diagnoses. In addition, disparate approaches to the reports between
laboratories visited adversely affected the number of examinations available for this
study. Studies focusing on the incidence of these tumors are essential in order to
determine the evolution of CNS tumors over time.
Nevertheless, our epidemiological description of CNS tumors in the state of Sergipe
between 2010 and 2018 is consistent with the data from other recent studies. This
characterization also shows similarities with a study conducted on the population
of Sergipe between 2000 and 2010 regarding age groups, locations, and most prevalent
histological types[25]. The annual average numbers of benign and malignant tumors found were similar, in
absolute numbers, to the incidence of malignant CNS tumors estimated for 2020 through
the RCBP of Aracaju, Sergipe. This may be related to the low rate of histopathological
diagnosis of these tumors in the state of Sergipe[27]. In Brazil, CNS tumor registries do not present the necessary standardization for
more reliable data analysis[37]. Therefore, more studies on pathological reports are essential for evaluating the
epidemiological evolution of CNS tumors in Sergipe. Studies on the incidence of these
tumors and possible associated risk factors are relevant approaches. Knowledge of
the evolution profile is vital for optimization of approaches used among the patients
affected.
