Clinico Pathological Study of Central Nervous System Neoplasms

The central nervous system consists of brain and spinal cord invested with meninges. It is made up of two types of cells, Nerve cells or neurons which show numerous long processes and Glial cells which are the supporting cells of the nervous system, which occupy the space between neurons. Four principal types of neuroglial cells are recognized: Oligodendrocytes, Astrocytes, Microglial cells and Ependymal cells. Central Nervous System (CNS) tumors account for 85% of brain tumors and 15% of spinal cord tumors, however metastatic tumors are usually extradural. Brain tumors are the second most common solid tumors in children next to Leukemia. Medulloblastoma is the commonest tumor among the pediatrics age group. Risk factors affecting brain tumors still persist unclear. Neoplasms of central nervous system accounts for approximately 1% of tumors of the human body, and they can be primary or secondary (metastatic), benign or malignant, and intraaxial or extra-axial. Neoplasms of the CNS can occur in both adults and pediatrics populations. Although adult and children may experience similar tumors, their incidences vary greatly with age. To study the spectrum of central nervous system space occupying lesions and the grade of neoplasms according to the guidelines provided by the World Health Organization (WHO). To correlate the diagnosis of these lesions with radiological findings in certain tumors, special stains and Immunohistochemistry were applied wherever needed. Original Research Article Priya et al.; JPRI, 33(21B): 64-76, 2021; Article no.JPRI.66773 65


INTRODUCTION
The central nervous system (CNS) is made up of the spinal cord, brain and meninges. The human nervous system is formed by the specialized network of cells called neurons. The neurons are responsible for the ability to receive, store and transmit information. Intracranial space occupying lesions are the important cause of neurological morbidity [1,2]. CNS tumors are well known for their life threatening behavior; hence the malignant potential is of two types, anatomic and biologic. Anatomic lesions are close to the vital centres and are deeply settled that could not be reached by physician, and it developed until it become fatal. Biologic lesions are violent tumors that rapidly growing with the resulting of neurophil attack and damage. CNS tumors do not fix in to the common meaning of malignancy as they rarely spread outside the chief locality [3].
Among the top ten causes of cancer deaths in the world, a brain tumor remains high. According to the Central Brain Tumor Registry of United States (CBTRUS), the whole frequency was found to be 21. 97 per 100,000 persons. Brain tumors are the second most common solid tumors in children next to Leukemia. Medulloblastoma is the commonest tumor among the paediatric age group. Risk factors affecting brain tumors still persist unclear. Radiation contact, persons working in metal, rubber industries and family history of brain cancer are found to elevated the risk of brain tumor [4,5,6]. Increasingly sophisticated radiological investigations are available for diagnosing the brain tumor, but these modalities are harmonizing to the finding, not for assenting. These imaging techniques can tell us the probable diagnosis only [7,8,5,6,9,10]. The confirmation of diagnosis is done by histological examination of the tissue biopsy. Hence histopathology remains the gold standard for diagnosis.
The tumors are graded according to the modified 2007 WHO classification criteria. Grading is essential for the management plan and treatment strategy [11][12][13][14][15]. In this era of clinical research Immunohistochemistry play a vital tool to help in giving the confirmatory diagnosis as the cell of origin is found out. The diagnosis of certain CNS tumors is very challenging; in such instances immunohistochemistry is used. It is found to be very useful in arriving at final diagnosis. [16][17][18][19][20][21][22][23]

MATERIALS AND METHODS
This study was conducted in the Department of Pathology, Sree Balaji Medical College and Hospital, Chennai during the study period of April 2015 to September 2016. All the specimens received from the department of Neurosurgery, Sree Balaji Medical College and Hospital, Chennai were studied and 95 cases were included in this study.
Biopsies were carried out for aggregate measuring 0.5cc to 4cc in the specimen. A thorough history with clinical symptoms and signs were noted. Site of the tumors were noted, and correlated with the imaging findings.
All the specimens were received in formalin and fixed in 10% neutral formalin. 4 micron thickness sections were made followed by routine haematoxylin and eosin staining.
During the study period between April 2015 and September 2016, all the cases received from the department of neurosurgery, Sree Balaji medical college and hospital were analysed and 95 cases were included in the study conducted at the department of Pathology, SBMCH. Out of 95 cases of CNS neoplasms, 49 cases were Astrocytomas which is found to be the most common neoplasm constituting about 52% of cases, followed by 19 cases of Meningiomas constituting 20%, 12 cases (13%) of Nerve sheath tumors were seen, 4 cases of Medulloblastoma followed by 4 cases of Pituitary adenoma (4%) and 3 cases of Ependymoma constituting 2%. We reported one case each in Oligodendroglioma, Craniopharyngioma, Primitive Neuro Ectodermal Tumor and Lymphoma constituting 1% each.

Overall Site of Occurrence of CNS Tumors
In our study we found that most being the frontal lobe with 27 cases followed by 20 cases in parietal lobe (2%), 9 (10%)cases were seen in Temporal lobe.8 cases (8%) were seen in CP angle and 8 (8%) spine,5 cases (5%) in supra sellar region, 4 (4%)
The tumors are graded according to the following features, it includes midline, edema, signal heterogeneity, necrosis, haemorrhage, borders and mass effect 34 . ; Article no.JPRI.66773 ital lobe, 3 cases (3%) in posterior fossa, and 2 cases (2%) in sphenoid wing as in The tumors are graded according to the following features, it includes -crossing midline, edema, signal heterogeneity, necrosis, haemorrhage, borders and mass Radiologically Low grade glioma appears hypo intense on T1WI, hyperintense on T2WI with mass effect and no enhancement. High grade glioma contains necrosis , haemorrhage, edema with mass effect. Glioblastoma shows irregular margins, haemorrhage and central areas of necrosis surrounded by extensive edema Among the 7 cases, 3 were radiologically diagnosed as Metastasis as it has ring enhancement, in histo pathology it came out as GBM. Two cases were reported as tuberculoma in radiology, out of which one came out to be high grade glioma and the other came out to be low grade glioma in histopathology. Two cases were diagnosed as Meningioma in radiology as it is attached to the dura, came out to be Astrocytoma in histopathology. Hence radiology was found to be useful in giving the preoperative diagnosis in CNS neoplasms and histopathology was found to be the gold standard in diagnosing the CNS neoplasms.

GRADE I
Among 49 cases (52%) of astrocytomas 4 cases (8%) were Pilocytic astrocytoma which comes under Low grade or Grade I astrocytoma. Histopathology showed the presence of Rosenthal fibres and eosinophilic granular

Chart 5. Site of occurrence of CNS tumors
Radiologically Low grade glioma appears hypo intense on T1WI, hyperintense on T2WI with mass effect and no enhancement. High grade glioma contains necrosis , haemorrhage, edema ffect. Glioblastoma shows irregular margins, haemorrhage and central areas of necrosis surrounded by extensive edema 34 . Among the 7 cases, 3 were radiologically diagnosed as Metastasis as it has ring pathology it came out as GBM. Two cases were reported as tuberculoma in radiology, out of which one came out to be high grade glioma and the other came out to be low grade glioma in histopathology. Two cases were diagnosed as Meningioma in radiology as it is attached to the dura, came out to be Astrocytoma in histopathology. Hence radiology was found to be useful in giving the preoperative diagnosis in CNS neoplasms and histopathology was found to be the gold standard in diagnosing

Features of Astrocytomas Seen in Our Study
Among 49 cases (52%) of astrocytomas 4 cases (8%) were Pilocytic astrocytoma which comes under Low grade or Grade I astrocytoma. Histopathology showed the presence of nd eosinophilic granular bodies among a delicate network of hair like cytoplasmic processes with micro cysts. No microvascular proliferation and no necrosis ( Fig .1)

GRADE II
Totally 13 cases (26%) were reported as grade II tumors or Diffuse astrocytoma.

Gemistocytic astrocytoma
We reported five cases of Gemistocytic astrocytoma, a variant of diffuse astrocytoma. Microscopy showed tumor cells with eosinophilic cytoplasm and nuclei pushed towards the periphery with prominent nucleoli in a coa fibrillary background. Perivascular ly proliferation is seen (Fig. 2 ).

Anaplastic astrocytoma
We reported 13 (26%) cases in grade III astrocytomas according to the histopathological features .Microscopy showed acellular composed of hyperchromatic and pleomorphic nuclei arranged in sheets in a background of fibrillary stroma. Areas of proliferating capillaries, mitotic figures and microcystic degeneration are seen. No evidence of necrosis. (Fig. 3).  (Fig. 3).

Grade IV
Totally 19 cases were reported in grade IV with 15 cases of Glioblastoma multiforme and 4 cases of Gliosarcoma, a variant of GBM.

Glioblastoma multiforme (GBM)
Microscopy showed fragments of a cellular neoplasm composed of pleomorphic giant cells, anaplastic cells, epitheloid cells with hyperchromatic nuclei. There are areas of necrosis surrounded by tumor cells known as pseudo pallisading necrosis. Microvascular proliferation, tumor giant cells and atypical mitotic figures are seen (Fig. 4).

Gliosarcoma
Microscopy showed round to oval pleomorphic cells having open chromatin with prominent nucleoli arranged around blood vessels along with foci of spongiform cells. Excessive proliferation of blood vessels and extensive areas of necrosis were seen. Many foci showed spindle cells with hyperchromatic and elongated nuclei arranged in fascicles. Many mitotic figures are seen in both spindle cell component and glial component (Figs. 5, 6).

Immunohistochemistry
GFAP immuno staining was done in which only the glial components stains brown and the non gl ial component remains unstained (Fig. 7).

Special stain
Reticulin stain was applied to demonstrate the mesenchymal component, the staining was seen around individual tumor cells.

DISCUSSION
In the present study about 95 CNS neoplasms reported during April 2015 -September 2016 were included. In our study CNS tumors are most commonly seen in the age group of 41 -50 years with 24 cases (27 %), followed by 31 -40 years with 19 cases ( 19%). Least number of cases were seen in the first decade.
In our study astrocytomas are found to be more common in males with 32 cases (65% ) than in females with 17 cases (35% ) which is similar to the studies done by Das et al [4] and Intisar et al [4] who also showed an increase incidence in males.   and Sasidhar et al [6]. Incidence was found to high in females with 14 cases (74%) in our study which is well established in many studies.
The nerve sheath tumor falls next to Meningiomas in our study with 12 cases (13%). Schwannomas are found to be more common with 9 cases (75%) than Neurofibroma with 3 cases (25%) which is similar to the study done by Intisar et al40. In our study there is a male preponderance, which is similar to many studies.
Pituitary adenomas represents 10 -20% of all CNS neoplasms [11]. We reported 4 cases (4%) of pituitary adenomas with one in the first decade one in second decades and the other two in third and seventh decade respectively. Male Female ratio was found to be equal in our study.
Three cases of Ependymoma were reported in our study one in paediatric age group, one in the third decade and the other in fifth decade. We reported a single case of Myxopapillary Ependymoma in a 35 year old male at the level of L1-L2 level. One case of lymphoma was reported in our study in 35 year old female in the frontal lobe.
Brain tumors in children represent the second most common solid tumors in the children. According to CBTRUS study 4350 children were diagnosed with brain tumor per year14. The etiology was not known clearly, but ionizing radiation is thought to induce both benign and malignant gliomas and occasionally primitive neuro -ectodermal tumor (PNET).
According to Ron Modan et al most of the tumors are multifactorial with both genes and environment playing a vital role. A total of 13 cases (14%) of paediatric brain tumors occurred in our study. According to the CBTRUS study about 7% of the brain tumors are seen in children [14]. Incidence of childhood brain tumors are compared with other studies.
In our study 50 cases (53%) were seen in females and 45 cases (47%) were seen in males. Two cases were reported as Tuberculoma in radiology, in histopathology one came out to be high grade glioma and the other came out to be low grade glioma. 2 cases were diagnosed as Meningioma in radiology because of its attachment to the dura, it came out to be Astrocytoma in histopathology. Hence radiology was found to be useful in giving the preoperative diagnosis in CNS neoplasms and histopathology was found to be the gold standard in diagnosing the CNS neoplasms. This is in accordance with study done by Intisar et al 26.
Histopathological diagnosis and grading of brain tumors is the corner stone upon which the management plans and treatment depends. Despite of the great advancement in ancillary studies, histopathology remains an invaluable means in the grading and diagnosis of brain tumors. Out of 95 cases of CNS neoplasms, 49 cases were Astrocytomas which was found to be the most common neoplasm constituting about 52% of cases, followed by 19 cases of Meningiomas constituting 20%, 12 cases (13%) of Nerve sheath tumors were seen, 4 cases of Medulloblastoma followed by 4 cases of Pituitary adenoma (4%) and 3 cases of Ependymoma constituting 2%. We reported one case each in Oligodendroglioma, Craniopharyngioma, Primitive Neuro Ectodermal Tumor and Lymphoma constituting 1% each. Radiological findings along with special stains and Immunohistochemistry were found very helpful to get an accurate diagnosis under Histopathology examination.

CONCLUSION
In our study Medulloblastoma was found to top among all other tumors. According to the CBTRUS study Medulloblastoma does the most common malignancy in children that constitutes about 20% of all malignant tumors. Histopathological diagnosis and grading of brain tumors is the corner stone upon which the management plans and treatment depends. Despite of the great advancement in ancillary studies, histopathology remains an invaluable means in the grading and diagnosis of brain tumors.

CONSENT
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ETHICAL APPROVAL
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