The Spectrum of Central Nervous System Tumors at a Tertiary Care Center Primarily Serving a Rural Population

Background Central nervous system (CNS) tumors cause significant mortality and morbidity in all age groups. There was no data about the histological spectrum of all CNS tumors in the tertiary care center serving primarily the rural population of Uttar Pradesh.


Introduction
In India, central nervous system (CNS) tumors account for nearly 2% of all malignancies, and their incidence ranges from 5-10 per 100,000 population [1,2].CNS tumors are the second most common malignancy after hematopoietic neoplasm during childhood [3].They are the most common solid malignancy in the pediatric age group [4].
CNS tumors are rare, but they cause significant mortality and morbidity in all age groups.Despite extensive research, no specific risk factors have been identified in the majority of cases [5].Known risk factors, e.g., heritable genetic syndromes and exposure to ionizing radiation, are seen only in <10% of cases [6].Many brain tumors are histologically graded from one (I) to four (IV) according to the World Health Organization's (WHO) Classification.However, all brain tumors do not have a classification that runs from grade I to IV (for example, meningiomas are graded from I to III, and a few CNS tumors like hemangiomas are not graded).Histological grading is used for predicting the biological behavior of a tumor.WHO-grade I tumors generally show low proliferative potential, and there is the possibility of a cure with surgical excision only [7].WHO-grade II tumors also show low levels of proliferative activity, but they are infiltrative in nature.WHO-grade III tumors show histological evidence of malignancy (nuclear atypia, mitosis).WHOgrade IV tumors show malignant features and aggressive behavior, and they are mitotically active, necrosisprone, and associated with rapid disease evolution [7].
Glioblastoma multiforme (GBM) is a WHO-grade IV tumor with an invasive nature.Despite treatment, less than half of patients survive for more than a year [8].
However, with advances in surgical techniques, radiology, newer chemotherapy, and radiotherapy, treatment outcomes are being improved day by day [9].
To date, there is no data available for CNS tumors in the rural population in this region.This study will give insights into the histopathological spectrum of CNS tumors.This data will be useful for better patient care as well as for further research.

Materials And Methods
This study was conducted in the Department of Pathology, Uttar Pradesh University of Medical Sciences (UPUMS), Saifai, Uttar Pradesh, India.This was a retrospective, cross-sectional, hospital-based descriptive study.
The study duration was three years (from January 2017 to December 2019).The place of study was the Department of Pathology at UPUMS, Saifai.After obtaining approval from the ethical committee of the institution and after applying inclusion and exclusion criteria, a total of 115 biopsies of CNS tumors were retrieved from available histopathology records.The study included all the cases of CNS tumors (cases of brain and spinal cord tumors) that were presented in the Department of Neurosurgery.These surgical biopsies were received in the Department of Pathology and reported during the study period.All the nonneoplastic lesions (inflammatory and cystic lesions) were excluded.All inadequate/insufficient biopsies were also excluded.Case details, along with clinical and radiological records, were noted.
Gross and microscopic examinations were evaluated by the authors.Formalin-fixed paraffin-embedded tissue blocks/hematoxylin and eosine (H&E)-stained slides were retrieved.The H&E-stained slides were reviewed by the authors.After confirming the histopathological diagnosis, all the cases were classified and graded according to WHO Classification 2016.Thus, the histopathological spectrum of CNS tumors could be seen.Generally, many CNS tumors are histologically graded from one (I) to four (IV) according to their behavior.Histological grading is used for predicting the biological behavior of a tumor.Data was analyzed for histopathological spectrum and frequencies in different age groups and genders.

Results
In this study, we retrieved 115 cases of CNS tumors over three years.Of these, 113 cases (98.26%) were primary tumors, and only two cases (1.74%) were found to be metastatic (secondary tumors) (Table 1).The most common histological types were neuroepithelial tumors (53 cases, 46.08%).Out of 53 neuroepithelial tumor cases, 36 were astrocytic tumors.In astrocytic tumors, nearly half the tumors (17 out of 36 cases) were diagnosed as GBM (WHO grade IV).The second most common CNS tumor category was meningeal tumors (32 cases, 27.82%), followed by tumors of the cranial and paraspinal nerves (16 cases, 13.91%).Meningothelial meningioma (nine cases) was the most common meningioma found in this study (Table 2).

Sl.
No  In total, 26 cases of meningioma were found at WHO grade I. Two cases of atypical meningioma (grade II) and one case of rhabdoid meningioma (grade III) were also diagnosed.Astrocytic tumors showed WHO grade I, II, III, and IV tumors in two cases (5.5%), 12 cases (33.3%), four cases (11.1%), and 18 cases (50%), respectively.In grade IV tumors, the most common tumors were glioblastoma with 17 cases, followed by medulloblastoma with four cases, and gliosarcoma with one case (Table 2).The morphological features of common CNS tumors in our study are described in Figure 1.In this study, the M/F ratio was 0.7, i.e., overall, females were more affected with 68 cases (59.13%), while the number of male patients was 47 cases (40.87%).In meningioma, females were three times more affected (22 out of 29 cases, 75.86%) than males.Tumors of the cranial and spinal nerves also showed female gender predilection in 11 out of 16 cases (68.75%).Cases of neuroepithelial tumors were distributed equally among both genders (Table 3).

TABLE 4: Age-wise distribution
In our study, a total of 18 patients with CNS tumors were found in patients <20 years of age, of whom eight were males and 10 were females (  The most common CNS tumors encountered in this age group (<20 years) were ependymoma and medulloblastoma, with four cases each.The most common location of tumors was the posterior fossa.

Discussion
CNS tumors are rare, but they are the second most common malignancy in children after leukemia.In this study, we reviewed 115 cases of CNS tumors retrospectively to categorize them according to WHO histological grades.
In a statistical report by Ostrom et al. (2022), the most common malignant brain tumor was glioblastoma (14.2% of all CNS tumors) [12].Similarly, glioblastoma was the most common malignant tumor in our study, with 17 cases (14.78% of all CNS tumors and 47.2% of astrocytic tumors), and the median age was 42 years.Thambi et al. (2017) stated that the median age for glioblastoma was 55.5 years [13].Interestingly, in this study, we have reported glioblastoma in a 17-year-old male.
Many studies showed male patients' predominance in CNS tumors (Table 6), while in this study overall, females were more affected than males in almost all histologic categories of CNS tumors, especially in meningioma, as 75.86% of cases were female.Similarly, meningiomas were seen more commonly in females by Sen et al. (2022) [11] and Lee et al. (2010) [14].In this study, the M/F ratio was 0.7.Thambi et al. (2017) also found a lower M/F ratio (0.9) [13].In a study by Jaiswal et al. (2016) [15], the most frequent tumor histology among children was astrocytomas (25.1%), followed by embryonal (20.6%), and ependymal tumors (14.8%).[10,11,13,17] Astrocytic tumors and cranial and paraspinal nerve tumors were three cases each (16.6%).We compared our results with those of other similar studies, and the comparison results have been tabulated (Table 6).
However, our study has limitations because it was conducted in one center only.Biopsies of patients undergoing surgery in the hospital are included in the study, so this may not be representative of the entire population/rural population of this region.

Conclusions
Through this study, we came to know about the histopathological spectrum of CNS tumors in the rural region of Uttar Pradesh.We observed the frequencies of different histological types with their WHO grading, sex, and age distribution.This study provided relevant data that can be used for academic information and research.Further studies with the incorporation of advanced radiological investigation and immunohistochemistry are required for comprehensive research and better patient management.
any organization for the submitted work.Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

TABLE 1 : Primary and secondary tumors
CNS: central nervous system

TABLE 2 : Histological types of CNS tumors
In total, 107 cases from this study were graded according to the 2016 WHO Classification.Of these, 53 cases (49.53%) were found to be of grade I.While 25 cases (23.36%), seven cases (6.54%), and 22 cases (20.56%) were diagnosed as grade II, grade III, and grade IV, respectively.
CNS: central nervous system

TABLE 5 : Distribution of CNS tumors among children and younger age group (0-20 years)
SOL: space-occupying lesion; CNS: central nervous system