Key-words:
Brain tumors - histopathology - Madinah - World Health Organization 2007
Introduction
Primary brain tumors are a diverse group of neoplasms. More than 120 histological
types of these tumors have been classified by the World Health Organization (WHO).
Unlike other tumors, they are not staged and WHO have assigned a Grade (I through
IV) to predict their outcome. Conventionally, brain tumors are classified according
to the cell of origin or the site of origin such as neuroepithelial origin (including
astrocytic tumors, oligodendroglial tumors, oligoastrocytic tumors, ependymal tumors,
choroid plexus tumors, neuronal and mixed neuronal-glial tumors, pineal tumors, and
embryonal tumors), tumors of cranial nerves, tumors of the meninges, lymphomas and
hematopoietic neoplasms, germ cell tumors, tumors of the sellar region, and metastases.
A recent update in the WHO classification of brain tumor (2016) introduced a greater
reliance on molecular markers.[[1]] With the introduction of newer diagnostic modalities, including molecular studies,
the diagnostic accuracy has increased tremendously, and the exact histopathological
diagnosis of brain tumors has played vital part in the diagnosis, management, and
follow-up. The improvement in the diagnostic accuracy has played a major role in closing
the performance gap between diagnostic centers, reduce subjectivity, and increase
the standardization of diagnosis, which is crucial to plan an accurate treatment and
predict the prognosis.
Brain tumor, which is one of the most important cancers causing death, represents
the 17th most common cancer worldwide and accounts for 1%–2% of all tumors. Due to
a significant increase in the incidence of, and death rates from, brain tumor in many
developed countries, this type of tumor has special importance.[[2]] The peak rate of incidence of malignant brain tumors is seen in young children
and in elderly individuals of the fifth and seventh decades. The prognosis of this
tumor is relatively poor, and for all ages, the average survival period is 9 months,
and the 5-year survival rate is low, especially for the glioblastoma multiforme (GBM).
A benign neoplasm in the brain could have devastating effects and can turn lethal
due to their location, space-occupying effects, and predisposition to undergo malignant
transformation over a period of time.[[3]] Moreover, the incidence of brain tumors is increasing gradually throughout the
world, and this is mainly attributed to the development of newer diagnostic technologies
and the increased frequency of imaging tests.[[4]],[[5]] The exact etiology of the brain tumor by enlarge remains unknown; however, genetic
alterations, developmental abnormalities, and environmental factors have been reported
to play a vital part in the etiopathogenesis of these tumors. The histopathological
examinations are crucial for a definitive diagnosis and as a predictor of prognosis.[[6]]
The histopathological data on the brain tumor from our region is scant. Therefore,
the aim of the present study was to look at the histopathological pattern of these
tumors at King Fahad Hospital (KFH) in Madinah region over 12 years. The basic demographic
data were collected, and the tumors were studied under the guidelines of the WHO 2007
classification.[[7]]
Materials and Methods
The present study was a retrospective analysis of the data on brain tumors, which
involved the archival tumor blocks and clinicopathological data; and did not involve
any patient's personal information or any implication on the management protocol.
Hence, according to the principles of the Helsinki Declaration, no ethical approval
was required in our study. The study included 227 consecutive cases of brain tumors
diagnosed in the Pathology Department at a Tertiary Care Hospital in the Madinah region
of Saudi Arabia, over 12 years (January 2006–December 2017). After receiving the specimen
at our histopathology laboratory, the specimens were fixed for overnight in 10% buffered
formalin. After fixation, the tissue is processed, and blocks were prepared using
Leica automated tissue processor, and semithin (4-μm thick) sections were cut from
the tumor blocks and mounted over a glass slide and stained with routine hematoxylin
and eosin stains. Ancillary techniques such as special histochemical stain and immunohistochemistry
were used in suitable patients. All the sections were examined by a consultant general
pathologist and a second opinion was sought by a specialist neuropathologist in appropriate
cases. The histopathological diagnosis, age, sex, and other relevant clinical data
such as the site of tumor were collected from the patients' record. All the records
which did not include any of the above-mentioned variables were excluded. Nonneoplastic
and inflammatory lesions were also excluded. The tumors were reassessed and graded
according to the WHO 2007 classification of tumors of the Central Nervous System (CNS).[[7]] We have very limited resources and could not expect all the standard diagnostic
procedures, including molecular studies at our center. Thus, we have chosen the WHO
classification 2007, which was not based on the molecular study. As the objective
of this study was to address the histopathological pattern of brain tumors and basic
demographic and information; hence, no comparison was indicated between the parameters.
Thus, the statistical analysis was not performed in the present study. The findings
were tabulated in Microsoft Excel Worksheet and analyzed on the basis of histopathological
classification of the tumors, their frequencies, age, and sex distribution.
Results
A total of 227 consecutive patients with brain tumors were identified for 12 years;
122 (53.7%) patients were males, whereas 105 (46.3%) patients were females, with a
male-to-female (M:F) ratio of 1.2:1. The ages ranged from 1 to 90 years, with a mean
age of 42.9 years. In this study, the predominant age group affected was between 40
and 49 years (23.5%). There were only 24 (10.6%) cases of pediatric brain tumors (age
<18 years) in our study.
[[Table 1]] shows the number, percentage, mean ages, and sex distribution of our patients with
brain tumors. There were 70 (30.8%) cases of meningiomas, 66 (29.1%) cases of astrocytic
tumors, 17 (7.5%) cases of sellar tumors, 17 (7.5%) cases of metastatic carcinomas,
15 (6.6%) cases of medulloblastomas, 13 (5.7%) cases of oligodendroglial tumors, 9
(3.9%) cases of schwannomas, 7 (3.1%) cases of ependymal tumors, 4 (1.8%) cases of
hemangioblastomas, 3 (1.3%) cases of cavernous hemangiomas, 2 (0.8%) cases of lymphomas,
2 (0.8%) cases of central neurocytomas, and 2 (0.8%) cases of plasma cell tumors.
Among females, the most common diagnosis was meningiomas (40%); among males, it was
astrocytic tumors (42.6%) [[Table 1]] and [[Figure 1]].
Table 1: The number, percentage, mean ages, and sex distribution of our patients with brain tumors
Figure 1: Pie chart showing the incidence of various brain tumors
Meningiomas showed a female predominance (M:F ratio of 1:1.5), with a mean age of
47.7 years [[Table 1]]. The most common sites were the dura overlying the temporal and parietal lobes
of the cerebrum. The most common histological subtypes were the meningothelial type
(24.2%) and fibroblastic type (6.6%). There were 61 (87.1%) cases of Grade I meningiomas,
6 (8.6%) cases of Grade II, and 3 (4.3%) cases of Grade III.
Astrocytic tumors were the second-most common histological type in our analysis, representing
29.1% of the total percentages of cases. In contrast to meningiomas, astrocytic tumors
were more common in males than in females (M: F ratio of 2.3:1). The mean age of the
patients was 45.2 years. There were 3 (4.5%) cases of Grade I astrocytomas, 7 (10.6%)
cases of Grade II, 13 (19.7%) cases of Grade III, and 43 (65.2%) cases of glioblastomas
(Grade IV). The most common sites involved were the temporal and parietal lobes of
the cerebrum.
The third-most common histological diagnosis was for sellar tumors, of which 82.4%
were pituitary adenomas. The mean age of the patients with sellar tumors was 42.6
years, and the M:F ratio was 7:10. Craniopharyngiomas were less frequent sellar tumors,
accounting for 17.6% of the cases. Medulloblastomas showed a male predominance (M:F
ratio of 1.5:1) with a mean age of 16.5 years. The most common site was the cerebellum
(81.3%). Other less frequent brain tumors seen in our series were oligodendroglial
tumors, schwannomas, and ependymal tumors, which represented 5.7%, 3.9%, and 3.1%
of the total percentages of cases, respectively. Among mesenchymal tumors and hematopoietic
tumors, there were three cases of cavernous hemangiomas and two cases of CNS lymphomas,
respectively.
Of the 17 metastatic tumors, the most common histological type was adenocarcinomas
(14 cases, 82.3%). There were 2 (11.8%) cases of metastatic hepatocellular carcinomas
and 1 (5.9%) case of metastatic thyroid cancer.
Discussion
Brain tumors are a heterogeneous group of neoplasm, and the predominant types in the
adult population are glial neoplasms, meningioma, and metastasis. Globally, there
is a large variability in the trends of brain tumor diagnoses given the vast different
histological subtypes interpretation criteria and potential artifacts linked to newer
diagnostic modalities, therapeutic approaches, and registries practiced in different
countries. High morbidity and mortality are associated with these tumors, irrespective
of their nature and histological grades. The GLOBOCAN Project (2012) reported the
incidence of CNS tumors at 1.8% and the mortality rate at 2.3% worldwide (total incidence
age-standardized rate [ASR] of 3.4/100,000 and a mortality ASR of 2.5/100,000 worldwide).
In the developing countries, the incidence ASR of CNS tumors was reported to be 3.0/100,000,
and for mortality ASR, the estimate was 2.2/100,000. In addition, GLOBOCAN has also
described the sex-related data and showed that males have a higher CNS tumor incidence
ASR (3.9) compared with that of females (3.0) throughout the world.[[8]],[[9]]
Despite the growing burden of brain tumors throughout the world, the published data
available on the histopathological profile of brain tumors from our region in Saudi
Arabia is scant. Hence, in this baseline study, the author has tried to highlight
the frequency, demographic features, and histopathological profile of brain tumors
in a large cohort of 227 Saudi patients. The present study being a retrospective histopathology
laboratory-based research, it has the limitation of dependence on the data collection
efficacy and lack of statistical analysis. However, it has served the purpose of providing
basic demographic and clinicopathological data, which can be compared with available
studies in the literature. This study provides a primary baseline tool to workup for
future population targeted studies on brain tumors.
Saudi Arabia is the largest nation in the Middle East and the 12th largest nation
in the world, with an estimated population of 33 million. According to the most recent
Saudi Cancer Registry report showed that there are 329 new cases of brain cancer diagnosed
in 2014, accounting for 2.8% of total cancer patients and making it the 10th most
frequent cancer among males and females in the Saudi population. The five regions
with the highest brain cancer ASR were Riyadh region, followed by Jouf region, then
the Northern region, then the Eastern region, and Qassim region. Madinah region had
the lowest brain cancer ASR after Jazan, Hail, and Asir regions.[[10]]
An extensive search of the literature did not yield any independently published study
from our region; hence, no regional data are available for the comparison of our findings.
However, an article on the same topic from KFH, Dammam, Saudi Arabia, had a comparable
number of neuroepithelial brain tumor cases. In their study, the authors reported
all the neuroepithelial tumors according to the 2007 edition of the WHO classifications
of CNS tumors. They analyzed all the neuroepithelial tumor cases of the Eastern province
retrospectively from 2007. After excluding other brain tumors, such as metastases,
meningiomas, lymphomas, and tumors located in the pituitary gland, a total of 149
cases of neuroepithelial tumors were reported. We found similarities in the prevalence
of GBM cases in our study (43 cases) when correlated with the above study (48 cases).[[11]]
In this study, the predominant age group affected by brain tumors was between 40 and
49 years (23.5%). Regarding the pediatric population (age <18 years) in our study,
there were only 24 (10.6%) cases of pediatric brain tumors, of which 15 (6.6%) were
medulloblastomas, with a mean age of 16.5 years, and 3 (1.3%) were cavernous hemangiomas,
with a mean age of 12 years. However, when compared with data reported from the Central
Brain Tumor Registry of the United States (CBTRUS) between 2010 and 2014, the age
groups affected by brain and other brain tumors were older, only 14% <20 years, 28%
from 20 to 49 years, 31% from 50 to 69 years, and 27% >70 years.[[12]] Males were affected more than females in the current study (M:F was 1.2:1), and
this was in coherence with other studies.[[13]],[[14]] However, in meningiomas females outnumbered the males in our series (M:F 1:1.5).
A similar female preponderance was observed by Yeole,[[15]] Ghanghoria et al.,[[16]] and Masoodi et al.[[17]]
In the present study, the most frequently encountered intracranial tumor was meningiomas
which were accounted for 30.8% (70/227) of a total number of cases, followed by astrocytic
tumors 29.1% (66/227), metastatic tumors 7.5% (17/227), and pituitary adenomas at
6.2% (14/227). The high prevalence of meningiomas in our study is comparable with
findings of the CBTRUS [[11]] in the United States (35%), Das et al.[[18]] in Singapore (35.1%). Idowu et al.[[19]] in Nigeria (35%), Dho et al.[[20]] in the Republic of Korea (37.3%), and Nakamura et al.[[21]] in Japan (36.8%) where all of them reported meningiomas as the most commonly occurring
brain tumor in their series.
Contrary to our findings, few differences were observed with the studies from Croatia,
Italy, and Canada, which showed that glioblastomas were the most common tumor among
intracranial neoplasms.[[22]],[[23]],[[24]] Our findings also contrast with the study by Bangash [[25]] in Saudi Arabia, who reported that the most common tumors affecting adult Saudis
at King Abdul-Aziz University Hospital were metastatic brain tumors (28.5%), followed
by astrocytomas (20.7%), and pituitary adenomas (15.5%). Another less frequently occurring
tumor is our study was a pituitary adenoma. We found 14 (6.2%) cases of pituitary
adenoma in the present study. The frequency of pituitary adenoma was reported to be
lower than what observed by Masoodi et al.,[[17]] Das et al.,[[18]] and Bangash [[25]] they noted 11.3%, 11.8%, and 15.5% of cases, respectively.
In our series, the metastatic spread from a distant primary to the brain is 7.5% (17/227)
of total cases. The frequency of metastasis in our study is lower than that of various
previous studies. Bangash [[25]] from Western Saudi Arabia has reported a very high rate (28.5%) of metastatic tumors
in his study; in fact, metastatic tumors were the most common brain neoplasm in his
cohort. It has been postulated that the increase in the diagnosis of metastatic brain
tumors could be in part attributed to the presence of a well-established oncology
service at his institute. Among the 17 metastatic tumors, the most common histological
type noted was adenocarcinoma (14 cases, 82.3%), our findings are comparable to studies
done in Nepal and Korea.[[26]],[[27]] A detailed comparison of our demographic findings and histopathological types of
brain tumors with the previous national and international publishes literature is
summarized in [[Table 2]].
Table 2: Comparison of our findings of brain tumors with the previous national and international
publishes literature
This study has a few limitations. First, the sample was restricted to one tertiary
care government hospital, which might limit the extension of results to the general
population and provide a rough estimate of primary brain tumors in the Madinah region.
Second, being a retrospective histopathology laboratory-based research, it has the
limitation of dependence on the data collection efficacy and lack of a proper statistical
analysis. Finally, the sample size is relatively small, and it has not included the
recent WHO 2016 classification for the categorization of brain tumors.
Conclusion
This retrospective study on 227 consecutive Saudi patients established a baseline
of brain tumor pattern on the basis of histopathological experience at a tertiary
care hospital in Madinah, Saudi Arabia, and provides a platform to workup for future
population targeted studies. The highest incidence of brain tumors was observed in
patients between 40 and 49 years with a male preponderance (M:F = 1.2:1). The most
common histopathological type seen in our study of brain tumors were meningiomas,
astrocytic tumors, embryonal tumors, pituitary adenomas, and metastatic tumors. Our
recorded data match with that of the world literature and Saudi national studies with
some variations.[[29]]
