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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 5  |  Page : 175-181

Histological spectrum of central nervous system lesions at a tertiary care center in India


Spectrum of CNS lesions, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong, Meghalaya, India

Date of Submission11-Mar-2020
Date of Decision20-Jul-2020
Date of Acceptance02-Aug-2020
Date of Web Publication12-Oct-2020

Correspondence Address:
Jaya Mishra
Department of Pathology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences, Shillong - 793 018, Meghalaya
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ccij.ccij_39_20

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  Abstract 


Background: Central nervous system (CNS) lesions show considerable geographic and racial variations with respect to the incidence and their pattern of distribution. The histological spectrum of CNS lesions is broad and it varies among extremes of age groups. The study is aimed to determine the diversity of CNS lesions as well as to highlight the incidence and the histological spectrum of CNS lesions in a tertiary health center in India. Materials and Methods: A total of 238 CNS lesions were retrospectively analyzed in the Department of Pathology from October 2014 to November 2017. The specimens were processed by routine histotechniques, and immunohistochemistry (IHC) was performed whenever required. The diagnosis was confirmed by applying the existing World Health Organization classification. Results: Two hundred and thirty-eight cases of CNS lesions were analyzed, of which 33 (13.86%) cases were nonneoplastic, with the majority being cystic lesions 12 (36.36%). The neoplastic lesions comprised 205 (86.13%) cases, which included 200 (97.56%) primary and 5 (2.43%) metastatic lesions. Among the primary lesions, gliomas 57 (27.80%) were the most common followed by meningiomas 43 (20.97%) and schwannomas 37 (18.04%). Conclusion: The present study highlights the histological diversity of CNS lesions in both adult and pediatric age groups. Although with the advent of modern imaging techniques, a provisional diagnosis could be given to these diseases, histological examination with further utilization of IHC remains the gold standard in diagnosis and grading of all CNS lesions. This has further helped in management as well as the prognosis of these diseases.

Keywords: Central nervous system, gliomas, immunohistochemistry


How to cite this article:
Khonglah Y, Shangpliang D, Mishra J, Mustafa A, Kakoti A, Phukan P. Histological spectrum of central nervous system lesions at a tertiary care center in India. Clin Cancer Investig J 2020;9:175-81

How to cite this URL:
Khonglah Y, Shangpliang D, Mishra J, Mustafa A, Kakoti A, Phukan P. Histological spectrum of central nervous system lesions at a tertiary care center in India. Clin Cancer Investig J [serial online] 2020 [cited 2020 Dec 2];9:175-81. Available from: https://www.ccij-online.org/text.asp?2020/9/5/175/297998




  Introduction Top


“Intra-cranial space-occupying lesion” (ICSOL) is defined as any mass lesion in the cranial cavity with varied etiology such as infectious, neoplastic, inflammatory, or any vascular malformation.[1] The SOLs of the central nervous system (CNS) can have a serious clinical course even when they are inflammatory lesions or benign neoplasms. Their potentially life-threatening behavior results from their emergence in a confined space as well as their proximity to vital structures. Therefore, it is of great importance to establish an accurate diagnosis for timely neurosurgical intervention.[2] The tumors of the CNS account to be <2% of all malignancies. In India, they constitute about 1.9% of all tumors.[3] The pathologist plays a great role in differentiating between neoplastic and nonneoplastic mimickers since a varied number of nonneoplastic conditions can mimic brain tumors, both clinically and radiologically.

Multiple risk factors, including genetic mutations (Li–Fraumeni syndrome) and ionizing radiation, contribute to the pathogenesis of brain tumors, but the exact etiological agent and risk factors are still not clear.[2] Tumors of the CNS are histologically typed by the World Health Organization (WHO) as tumors of neuroepithelial tissue, peripheral nerves, meninges, mesenchymal nonmeningothelial tumors, lymphomas, germ cell tumors, and metastatic tumors.[4] The exact histopathological diagnosis of CNS tumors using techniques like the application of histochemical stain and immunohistochemistry (IHC) has played a major role in differential diagnosis and improving diagnostic accuracy, which is essential to predict the grading and prognosis.[3]

The histological spectrum of CNS lesions is broad and it varies among extremes of age groups. In developing countries like India, due to the privation of complete registration of newly diagnosed cases with local cancer registries, the precise tumor burden of such diseases goes unnoticed and underestimated. Thus, hospital-based prevalence databases are imperative for estimating the disease load.[4] The purpose of this study is to determine the diversity of CNS lesions as well as to highlight the incidence and the histological spectrum of CNS lesions in a tertiary care hospital in India.


  Materials and Methods Top


This retrospective study was conducted in a tertiary care hospital in India for 3 years from October 2014 to November 2017 on neurosurgical biopsies. The cases were diagnosed and characterized, where necessary using IHC and categorized according to the WHO 2016 classification. The inclusion criteria were cases of CNS tumors of all age groups. The tumors of the peripheral nervous system were excluded. With these criteria, a total of 238 cases of CNS lesions were studied, and their histological typing and grading were done.


  Results Top


In a total of 238 cases of ICSOL, 205 cases (86.13%) were neoplastic and 33 cases (13.86%) were nonneoplastic. The mean age was 36 (range: 23 days to 80 years) years. The peak incidence was seen in 31–40 years, which accounted for 52 (21.84%) cases. Males represented 121 (50.84%) of the study population, whereas 117 (49.15%) were female, with male-to-female ratio of (1.03:1) [Figure 1]. There were only 48 (23.41%) cases of pediatric brain tumors (age <18 years) in our study.
Figure 1: Gender distribution of intra-cranial space-occupying lesion

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During clinical examination, the majority of the patients presented with headache (61.34%) followed by visual deterioration, fever, epilepsy, vomiting, papilledema, altered sensorium, and loss of consciousness [Figure 2]. The frontal lobe was the most common site (21.00%) involved in most intracranial lesions. Some of the tumors involved >1 lobe of the brain. Other site-specific features such as scalp swelling and protrusion of meninges were seen in 16 cases.
Figure 2: Clinical presentations of intra-cranial space-occupying lesion

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Out of 205 (86.13%) neoplastic lesions encountered, 200 (97.56%) cases were primary and 5 (2.43%) were metastatic lesions. Among the primary tumors, gliomas (27.80%) constituted the largest category, followed by meningeal tumors (20.97%) and tumors of cranial and paraspinal nerves (18.04%) [Table 1].
Table 1: Age and sex distribution of neoplastic intracranial tumors

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Among the glial tumors, glioblastoma NOS grade IV was the most common histological subtype, with 27 (47.36%) cases. The youngest age of presentation of glioblastoma NOS was 21 years with a mean age at diagnosis being 42.38 years. Male-to-female ratio was 1:1.6. Other gliomas encountered in the present study were diffuse astrocytoma NOS-7 cases, pilocytic astrocytoma-5 cases, anaplastic astrocytoma NOS-4 cases, subependymal giant cell astrocytoma-1 case, gliosarcoma-1 case, pleomorphic xanthoastrocytoma-1 case, oligodendroglioma NOS-5 cases, anaplastic oligodendroglioma NOS-3 cases, oligoastocytoma-1 case, and anaplastic oligoastrocytoma-2 case.

The second predominant histological diagnosis was meningioma seen in 43 patients. The mean age of presentation was 44 years. Females outnumbered males in sex distribution with a ratio of 1:1.6. Meningothelial meningioma (WHO Grade I) was the most common histological subtype (53.48%) followed by transitional meningioma (WHO Grade I) 20.9%. Tumors of the cranial and paraspinal nerves constitute the third common histological pattern, all of which were Schwannomas. The mean age of diagnosis was 43.04 years with a male-to-female ratio of 1.4:1. Most of the tumors were located at the cerebellopontine angle.

According to the WHO grading, out of 57 gliomas, the majority were Grade IV tumors constituting 28 cases (49.12%) followed by 14 cases of Grade II tumors accounting for 24.56% [Table 2]. Among tumor of the meninges, Grade I meningiomas were predominant followed by Grade II [Table 3].
Table 2: WHO grade of gliomas

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Table 3: WHO grade of meningiomas

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On IHC, all the 57 cases of gliomas were positive for GFAP, including a single case of gliosarcoma, that showed positivity for Vimentin in the mesenchymal component with a strong Ki-67 proliferation index of >20% [Figure 3]. Among the 9 cases of mesenchymal tumors, 4 cases of hemangioblastoma were diagnosed and confirmed with CD 34 antigen highlighting the vascular component [Figure 4]. Two cases of germinoma were detected with IHC showing positive reaction for CD 117 and PLAP [Figure 5]. An interesting case of Lymphoma was initially diagnosed as the poorly differentiated tumor, and the patient was started on steroids. [Figure 6] shows the image finding of the tumor pre- and post-steroid therapy. On IHC, the tumor showed positivity for CD 45 and CD 20, while CD 3 was positive in the reactive T-cells. CD 7 positivity in a case of metastatic adenocarcinoma, documented that the primary was from the gastrointestinal tract [Figure 7]. Another eye-catching case was a case of low-grade chondrosarcoma of the left petrous apex, which was initially given as myxoid schwannoma with cystic degeneration on squash smears. The final diagnosis of low-grade chondrosarcoma was made on histology based on morphology and IHC that showed positive reaction for S-100 and Vimentin and were negative for Pan-CK and EMA [Figure 8]. Some of the histopathological patterns of CNS tumors encountered in the present study are shown in [Figure 9].
Figure 3: Gliosarcoma (a) H and E section showing spindled shape tumor cells with a high mitotic count. (b) GFAP positive in the astrocytic tumor cells (IHC). (c) Vimentin positivity in mesenchymal component (IHC). (d) Ki-67 proliferation index >20% (IHC) (×40)

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Figure 4: Hemangioblastoma (a) H and E section showing proliferation of variable-sized capillaries along with large neoplastic cells containing pink to clear cytoplasm. (b) CD 34 positive in the endothelial cells of thin-walled blood vessels (IHC) (×40)

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Figure 5: Germinoma (a) H and E section showing large tumor cells with clear cytoplasm and large round nucleus. (b) CD 117 positive in the tumor cells (IHC) (×40)

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Figure 6: Lymphoma (a and b) magnetic resonance imaging findings pre- and post- steroids. (c) H and E section showing atypical cells mostly in sheets (×20) (d-f) IHC showing CD45+, CD20+ and CD3, respectively (×40)

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Figure 7: Metastatic adenocarcinoma (a) H and E section showing tumor cells arranged in glandular pattern (×20) (b) CD 7 positive in the tumor cells (IHC) (×40)

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Figure 8: Low-grade chondrosarcoma (a) magnetic resonance imaging brain shows a multilobulated cystic lesion. (b) H and E crush smears showing sheets of tumor cells in a myxoid background (×10) (inset): Round cells with eccentric nucleus and abundant cytoplasm (×40) (c) H and E section showing lobules of cartilage (×10) (inset): Tumor cells present within a lacunae (×40) (d) S-100 positive in the tumor cells (IHC) (×40)

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Figure 9: (a) Astroblastoma: Tumor cells with expanded processes in pseudo-rosettes. (b) Oligodendroglioma: Tumor cells with coarse nuclear chromatin and ill-defined cytoplasm. (c) PXA: Spindled-to-globoid-shaped cells with atypical nuclei. (d) Meningioma: Ovoid-shaped tumor cells forming whorls. (e) Schwannoma: Depicts a typical verocay body. (f) Neurocytoma displaying homogeneous cell population with round nuclei and dispersed chromatin (H and E, ×40)

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Among the 33 nonneoplastic intracranial lesions, cystic lesions (36.36%) including dermoid cyst, arachnoid cyst, ependymal cyst, and hydatid cyst form the majority of the CNS nonneoplastic lesions followed by meningocele/meningomyelocele (30.30%). The highest number of nonneoplastic lesions was encountered in the third decade, with a female predominance [Table 4].
Table 4: Age and sex distribution of nonneoplastic intracranial lesions

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  Discussion Top


A retrospective epidemiological review of CNS neoplasms is of great importance for future research because it can demonstrate the changes in the spectrum of CNS lesions of a population, unveil the possible associated risk factors as well as indicating the potential therapy methods of various neoplastic and nonneoplastic lesions.

The present study shows that the 238 cases of CNS lesions share several features common with other published series [Table 5].
Table 5: Different types of central nervous system tumors and their prevalence in different studies

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In the current study comprising 238 CNS lesions, there were 205 (86.13%) neoplastic and 33 (13.86%) nonneoplastic lesions. Other studies in India conducted by Bajaj et al., Bhardwaj et al., and Nibhoria et al. showed 93.86% versus 6.14%, 92.85% versus 7.14% and 89% versus 11% distribution of lesions of neoplastic versus nonneoplastic pathology, respectively.[4],[8],[9]

The age range of brain lesion starts from the 1st year of life to 70 years. In studies conducted by Ahsan et al., in 2015, Butt et al., in 2005 and Ghanghoria et al., in 2014 showed an age range of 1–85 years, 1–69 years, and 2–80 years, respectively.[7],[10],[11] The male-to-female ratio is 1.03:1. A study conducted by Butt et al. and Ghanghoria et al. showed a ratio of 1.7:1 and 1:0.86, respectively.[10],[11] Despite some differences in ratios, all these studies show a higher affliction of the male gender, which is similar to our study.

Most of the cases in our study presented with multiple symptoms. Headache was the most common presenting symptom in this series, which is supported by the findings of all other studies.[12],[13] More than half of the patients suffered from visual deterioration. This can be explained by the late presentation of the patients to the physician. The common presence of fever can be explained by the fact that gliomas and abscesses constitute a significant proportion of SOLs in this study and could be responsible for the fever.[14] The frontal lobe was the commonest site (21.00%) of the involvement of CNS lesions. This trend was comparable to that reported by Pidakala et al., and Jalali and Datta.[15],[16]

The tumors have been categorized according to the 2016 WHO classification. In the present study, glial tumors (27.80%) were the most frequent type of intracranial tumors among all the primary CNS tumors, which was in agreement with all other observations.[4],[17]

With regard to the age distribution of glial tumors, the mean age of patients with astrocytic tumors was 25.60 years. These findings were comparable to those of Butt et al., and Anadure et al., who also reported that the majority of the astrocytic tumors were found in the younger age group.[1],[10] Glioblastoma NOS forms the largest subtype of astrocytic tumors (57.7%) with a mean age at diagnosis being 42.38 years. This is similar to the study conducted in Pakistan by Ahsan et al., but in contrast to international literature, where the mean age at diagnosis is 64 years.[7],[18]

In the present study, according to the WHO grading, out of 57 glial tumors, the majority were Grade IV tumors constituting of 28 cases (49.12%), followed by 14 cases of Grade II tumors accounting for 24.56%, which was in agreement with Kothari and Shah, where the majority were Grade IV with 11 cases (55%) out of 20 gliomas followed by Grade II with 7 cases (35%).[19] Hence, grading of glial tumors is important to predict their aggressiveness and prognosis to decide on the further treatment plan.

The mean age of patients diagnosed with meningiomas was 57.6 years (Europe), 59 years (United States), and 58.1 years (Asia).[19],[20],[21] The peak age group for this tumor type in the present series was considerably younger, at 44 years of age. This view is supported by other Indian studies who reported the average age of meningiomas to be 49.23 years (Jat et al.,) and 45.5 years (Nibhoria et al.,).[4],[19] Meningiomas showed female preponderance similar to other studies indicating that the growth of meningiomas is subject to hormonal influence.[22] Grade I meningioma was the most common (81.39%) according to the WHO grade. This was in agreement with Kalyani et al., and Anadure et al., who also reported Grade I meningiomas as the majority with (75%) and (87.5%), respectively.[1],[23]

The incidence of metastasis was (2.43%) in the present study, which was low as compared to other studies where the incidence was from 10% to 12%.[16],[24] In comparison, Ahsan et al., Chen et al., and Nibhoria et al. also reported a low incidence of only 4.9%, 5.1%, and 5.6%, respectively, of CNS tumors with secondary deposits.[4],[5],[7] As expected, metastatic tumors occurred between 51 and 70 years, comparable to most studies in the literature.[4]

Cystic lesions (36.36%) were the most common nonneoplastic lesions encountered in the present series. This was similar to studies conducted by Rathod et al., and Butt et al., who also observed similar findings.[10],[25]


  Conclusion Top


The present study highlights the histological diversity in CNS lesions in both adults and the pediatric age groups. Although with the advent of modern imaging techniques, the provisional diagnosis could be given to these diseases, histological examination with further utilization of IHC remains the gold standard in diagnosis and grading of all CNS lesions. This has further helped in management as well as the prognosis of these diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Full text]  
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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