Histopathological analysis of central nervous system tumors; an observational study

Background: Though the central nervous system tumor comprises ~2% of all the tumors, an overall increase has been observed especially in less developed countries. This increase in the incidence may be due to exposure of population to various risk factors or improved diagnosis with advancement in the ancillary studies. This study aims to provide a single centre histopathological spectrum of this type of tumor.


INTRODUCTION
The burden of cancer is increasing worldwide despite advances for diagnosis and treatment.1  Population based cancer registration provides an essential base for cancer control, providing information not only on incidence and survival but also facilitating confirmation of effectiveness of interventions.Hospital-based registries and even pathologybased registries also can make important contributions. 2   Though the tumors of the central nervous system (CNS) constitute approximately 2% of all malignancies, the associated morbidity and mortality and the significant proportion of affected young and middle-aged individuals has a major impact in life years compared to other

Keywords:
Astrocytoma; CNS; Embryonal tumors; Meningioma; Pituitary adenoma; WHO grade; malignancies. 3Moreover, these tumors are in increasing trend.An overall increase has been observed throughout the world, especially in less developed countries. 4The importance of descriptive data on the full spectrum of primary brain and CNS tumors has been previously recognized. 5The current study aims to evaluate and provide overview of descriptive epidemiology of CNS tumors in a single centre over a 3 year study period.Pathological classification of brain tumors is the corner stone upon which the management plan and treatment strategy depends. 6

MATERIALS AND METHODS
This is a retrospective cross-sectional study performed in the Department of Pathology at Annapurna Neurological Institute & Allied Science, Maitighar, Kathmandu, Nepal.This study was conducted in the histopathology samples received from April 2013 to Jan 2016.Ethical clearance was obtained from institutional review committee.The variables entered in the database were histopathology number, name, age, histopathological diagnoses, site of the tumor and tumor grade.All the histopathologically proven tumor specimens of CNS tumor received in the given time frame were included in the study.The specimens received were processed by fixing, dehydration, and clearing followed by impregnation with wax.The wax blocks were cut in 5-6 μ sections & stained by hematoxylin and eosin stain.The diagnoses were made on histological examination of the processed tissue.In our study the various lesions were studied and classified according to World Health Organisation (WHO) classification (2007).The 2007 WHO classification presented as the standard for the definition of brain tumors to the clinical oncology and cancer research communities worldwide. 7e World Health Organization classifies CNS tumors based on cellular origin and histologic appearance. 8Neuroglial tumors account for more than 80 % of primary brain tumors and derive from astrocytes, oligodendrocytes, or ependymal cells.Gliomas are divided into four grades; grades I and II tumors are low grade, whereas grades III and IV tumors are high grade. 9Data were analysed using SPSS version 21.0.

RESULTS
A total of 221 brain and CNS tumors (125 females and 96 males) were retrieved retrospectively from the registry during the time duration specified.According to the cell of origin, 88 cases were of neuroepithelial origin and 133 cases were non-neuroepithelial origin.
The age ranged from 6 months to 83 years with a mean age of 43.77 years.The age group ranging from 21-40years most commonly suffered from these tumors (n = 81; 36.7%),followed by 41-60 years (n=79; 35.8%), >60 years age (n=41; 18.6%) and the least common was age <20 years (n=20; 9.0%) CNS tumors in this study were most frequently encountered in the cerebrum comprising of 98 cases (44.3%) out of which 49 of them were situated in the frontal lobe, followed by the sellar region comprising of 44 cases (19.9%).
The most common tumor in this study was meningioma comprising of 67cases (30.3%).Astrocytic tumor comprised 57cases (25.7%) and third most common pituitary adenoma comprised of 30 cases (13.6%).The number of individual tumor in detail is tabulated.Table 1 and 2 As the CNS tumors of pediatric age group are considered to have its own spectrum, children of age group range 0-20 years were analyzed in our study as well.There was male preponderance with 14 males and six females, M:F=2.In our study there were 13 cases of metastatic carcinoma among which three were squamous cell carcinoma, Adenocarcinoma, ductal carcinoma, adenoid cystic carcinoma comprised one each however; eight were categorized as metastatic carcinoma and was sent for the identification of primary site with the help of immunohistochemistry.Other tumors like oligodendroglioma, craniopharyngioma, embryonal tumors and ependymomas were seen in different proportions.

DISCUSSION
The present study comprised of 221 CNS tumors irrespective of age, from a single centre and was categorized according to the recent WHO classification. 8

Distribution of CNS tumors by sex and age group
In our study male to female ratio was M:F= 1:1.comparable with other worldwide studies.Ghanghoria S et al had similar findings in their study comprising of 41.54% of meningioma. 13Lee et al 14 in Korea and Jazayeri SB et al 15 in Iran also observed that most common tumor was meningioma (31.2% and 27.8% respectively).However, our finding is contrasting with the first study conducted in Nepal.Aryal G et al noticed that the most frequent type of CNS tumor was astrocytoma (38.6%) followed by meningioma (14%). 16Similarly, a study conducted by Wiemels J et al showed the prevalence of pathologically confirmed meningioma to be low, reasoning that a proportion of meningioma are not surgically managed, these estimates may be low. 17ningioma showed female predominance in studies of Nibhoria S et al 11 and Thambi R 18 similar to our findings.
As mentioned earlier the most common histological subtype was transitional meningioma and meningothelial type which corroborated with the data of Thambi R et al in which transitional meningioma was followed by meningothelial type in frequency.There were 87.5% of grade I meningioma followed by other grades in her study whereas we encountered 98.5% of grade one meningioma and a single case was of grade II meningioma. 11,18e second most common astrocytic tumors (25.7%) was also a relatable finding to Thambi R et al (25%). 18The peak age group of this tumors was 21 to 40 years according to study conducted by Ayral G et al which is below our peak range of 41-60 years. 16The reason behind this contrasting finding in the same geographical area may be due to the changing time trends of the tumor and should be evaluated and calculated in depth by epidemiological surveys in other institutions of our country.GBM comprised the highest number of astrocytic tumor with frequency of 31.4%, 50.5% in other studies comparable to our finding of 47.4 percent. 10,16is WHO grade IV tumor was seen to be most frequent in the age group 41 to 60 years with a male preponderance.Similar results were obtained in various studies. 4,15,19I : 110.3126/jpn.v%vi%i.20892 3:1 which was contrary to the ratio of overall tumor.The DOI : 110.3126/jpn.v%vi%i.20892Kakshapati T et al.
3 showing female preponderance (56.5 %) which is similar to study in Singapore conducted by Das A et al10 with female occupying 52.6% however, findings of Nibhoria S et al11 was conflicting with the ratio of M:F= 1.2:1.The age group of patients with CNS tumors also corroborated with studies like that of Krishnatreya M et al in which the highest number of patients was seen in the age-group of 20-39 years and 21-40 years in our study.12Pattern of common CNS tumorMeningioma was the commonest tumor 30.3% which was DOI : 110.3126/jpn.v%vi%i.20892

Figure 3 :
Figure 3: Photomicrograph showing microscopic view of medulloblastoma with small round tumor cells with a Homer-Wright rosette (HE stain; X200).

Table 5 : 20 Figure 4 :
Figure 4: Bar diagram showing relative frequency of various WHO grade according to age group

20892 Histopathological analysis of central nervous system tumorsTable 1 : Sex-wise distribution of CNS tumor
. DOI : 110.3126/jpn.v%vi%i.In the cases of meningioma, there was female preponderance with M: F= 1:3.7) (14 males and 53 females) andshowed increased frequency in age group 3 (41-60years).As depicted in table 3, the meningothelial and transitional meningioma comprised of 26 cases each (38.8 %) and psammomatous meningioma comprised of 6 cases (9%).Astrocytic tumor showed male preponderance with male to female ratio of 1.4:1.It was encountered most frequently in the age group of 21-40years.Among astrocytic tumor 27 cases (47.4%) were of glioblastoma multiforme (GBM) seconded by diffuse fibrillary astrocytoma 11(19.3%)cases.(Table4)Pituitaryadenoma was third in proportion with total case of 30 (13.6%), showed equal sex predilection and age propensity to clinically manifest among the age group of 41-60 years.Among the studied total 221 CNS tumors, in 171 cases, it was possible to grade the tumors according to the WHO classification.The frequency of WHO grade I tumor was considerably higher comprising 94 cases (55%),WHO grade II tumor was 34 cases (19.9%),WHO grade III tumor was 10 cases (5.8%) and WHO grade IV tumor, 33 (19.3%) cases.In this study, WHO grade III tumor was the least , which is shown in bar diagram.(fig.4)WHO grade IV tumor was higher in age group of 41-60 years (42.42%)whereas WHO grade I, II and III tumor showed preponderance in age group 21-40 years (38.9%,61.7% and 60% respectively)as depicted in figure 4.

Table 4 : Relative frequency of astrocytic tumors according to age
The overall WHO grade IV tumor here was found to be highest in age group of 41-60 years (42.42%).A study conducted by Chen L et al in china also revealed the data of WHO grade III and IV being most frequent in the age group 40-49 and 50-59 years.In both of the studies the oldest age group did not show propensity towards the highest grade of tumor.4