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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 4  |  Issue : 3  |  Page : 54-56

Diagnostic challenges in epithelioid glioblastoma of the cerebellum: A case report


1 Department of Pathology, Government Medical College and Hospital, Chandigarh, India
2 Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Neurosurgery, Government Medical College and Hospital, Chandigarh, India

Date of Submission06-Sep-2021
Date of Decision23-Sep-2021
Date of Acceptance27-Sep-2021
Date of Web Publication11-Nov-2021

Correspondence Address:
Dr. Phiza Aggarwal
Department of Pathology, Government Medical College and Hospital, Sector-32, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_13_21

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  Abstract 


Epithelioid glioblastoma (eGB) is an uncommon morphological variant of isocitrate dehydrogenase wild-type GB that commonly presents as a cerebral mass in young adults and children. Here, we report the case of a 22-year-old man who presented with a cerebellar tumor. With the provisional diagnosis of pilocytic astrocytoma and adult medulloblastoma, he underwent suboccipital craniotomy with gross total excision of the tumor. On histopathological examination, he was diagnosed with eGB. Cerebellar presentation of eGB is a rare event that has not been previously described in the literature. The present case also highlights the need for differentiating eGB from its morphological mimics by carefully interpreting histopathological and immunohistochemical examination findings.

Keywords: Adult medulloblastoma, case report, cerebellar tumor, epithelioid cells, isocitrate dehydrogenase wild-type glioblastoma, pilocytic astrocytoma


How to cite this article:
Aggarwal P, Chatterjee D, Gupta VK, Gupt R. Diagnostic challenges in epithelioid glioblastoma of the cerebellum: A case report. Glioma 2021;4:54-6

How to cite this URL:
Aggarwal P, Chatterjee D, Gupta VK, Gupt R. Diagnostic challenges in epithelioid glioblastoma of the cerebellum: A case report. Glioma [serial online] 2021 [cited 2021 Dec 3];4:54-6. Available from: http://www.jglioma.com/text.asp?2021/4/3/54/330194




  Introduction Top


Glioblastoma (GB) is the most frequent malignant brain tumor in adults and accounts for approximately 45%–50% of all primary malignant brain tumors. Based on the presence or absence of point mutations in isocitrate dehydrogenase (IDH) 1 and 2 genes, GBs are classified as IDH mutant-type and IDH wild-type GBs, respectively. IDH wild type is the major subtype accounting for 90% of all GBs. Histologically, GB is a World Health Organization (WHO) Grade IV tumor of astrocytic lineage and is characterized by marked cellular atypia, increased mitotic activity, microvascular proliferation, and necrosis. It commonly affects adults aged over 50 years and has a poor prognosis.[1]

Epithelioid GB (eGB) is a rare morphological variant of IDH wild type that affects young adults and children and is associated with a shorter survival rate. It arises predominantly in the cerebral cortex and diencephalon. Besides features of a Grade IV tumor, eGB is characterized by uniform population of medium-to-large size, round-to-polygonal epithelioid cells that are arranged as diffuse sheets. Owing to its histopathological picture, the tumor mimics other primary astrocytic neoplasms and even metastasis, thus possibly posing a diagnostic challenge for pathologists. BRAF V600E mutation is observed in 50% of eGB cases, which may aid in diagnostic confirmation.[2] To the best of our knowledge, cases of eGB in the cerebellum have not been reported to date in the PubMed literature. Here, we report a case of cerebellar eGB in a young man and describe key histopathological features that help differentiate eGB from other diagnostic mimics.


  Case Report Top


A 22-year-old man with progressively deteriorating sensorium, nausea, vomiting, and unsteady gait for 15 days presented to the surgical emergency department. Noncontrast brain computed tomography revealed a space-occupying lesion, measuring 3.3 cm × 2.8 cm, in the left cerebellar hemisphere with features suggestive of a hydrocephalous. Considering his presentation, a ventriculoperitoneal shunt was placed, following which his sensorium improved. Magnetic resonance imaging revealed a well-defined mixed signal mass lesion, measuring 3.3 cm × 3.9 cm × 3.2 cm, with internal hemorrhage involving the left inferior cerebellar hemisphere. The mass was observed crossing the midline and involving the parasagittal aspect of the right cerebellar hemisphere [Figure 1]A and [Figure 1]B. On the basis of clinicoradiological findings, the differential diagnoses of pilocytic astrocytoma and adult medulloblastoma were made. The patient underwent surgical intervention in which suboccipital craniotomy with gross total excision of the tumor was performed. Hematoxylin and eosin-stained sections of the excised specimen showed an infiltrating tumor in the brain parenchyma arranged as dyscohesive sheets [Figure 1]C. The tumor cells predominantly had epithelioid morphology and showed cytoplasmic clearing at places [[Figure 1]C Inset 1]. Few giant cells, increased mitotic activity, microvascular proliferation, and areas of necrosis were also noted [[Figure 1]C Inset 2]. Perivascular lymphoid infiltrate and brisk tumor-infiltrating lymphocytes were also noted. The histological features were highly suggestive of a high-grade astrocytic tumor without any evidence of embryonal morphology. Reticulin staining did not show any pericellular reticulin network. Immunohistochemical analysis revealed focal but strong positivity for GFAP and strong cytoplasmic positivity for S-100 and vimentin. The tumor cells showed dense granular cytoplasmic positivity for BRAF V600E mutant protein and complete retention for INI1 protein [Figure 2]. Immunohistochemical examination findings were negative for CK, SMA, chromogranin, HMB45, and p53. The characteristic morphology of the tumor together with immunohistochemical findings favored the diagnosis of eGB. The patient showed signs of improvement after surgery. However, few days later, he developed multiple supratentorial infarcts and died.
Figure 1: Magnetic resonance and histology images. (A and B) Contrast-enhanced sagittal and axial magnetic resonance images showing a heterogeneously enhancing intra-axial mass lesion with areas of necrosis involving the left inferior cerebellar hemisphere with extension to the right side (black arrows). (C) Section showing a tumor infiltrating the brain parenchyma and arranged as dyscohesive sheets (black arrow) (×20, hematoxylin and eosin staining). Inset 1 shows epithelioid morphology of the tumor cells (×40, hematoxylin and eosin staining). Inset 2 shows large areas of necrosis in the tumor (black arrows) (×20, hematoxylin and eosin staining)

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Figure 2: Immunohistochemical analysis of epithelioid glioblastoma (×20). (A) Tumor cells (black arrow) show patchy but strong positivity for glial fibrillary acid protein. (B and C) Tumor cells (black arrow) show diffuse and strong positive expression for S-100 and vimentin. (D) Tumor cells (black arrow) show complete retention of INI1 expression. (E) Tumor cells (black arrow) show diffuse strong cytoplasmic positivity for BRAF

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We have only diagnosed this case. It does not involve any kind of research activity or clinical trial. Hence, ethics approval is not required. The need for written informed consent was waived owing to the retrospective nature of the study.


  Discussion Top


eGB is an uncommon variant of IDH wild-type GB and is recognized in the 2016 WHO classification update of central nervous system (CNS) tumors.[2] It is a high-grade diffuse astrocytic tumor with a predominant population of closely packed epithelioid cells. The tumor has a predilection for children and young adults as opposed to conventional GB. In a case series of 24 patients by Chatterjee et al.,[3] the mean age of patients with eGB was 29.9 years, with an equal male-to-female ratio.[3] Most eGBs occur in the cerebral cortex and diencephalon. The tumor in the present case was located in the cerebellum, which is a rare site for eGBs. In addition to the features of grade IV GBs, the tumor is characterized by diffuse sheets of epithelioid cells. According to the WHO, the epithelioid cells should constitute the predominant component of the tumor tissue in order to diagnose it as an eGB; however, definite cutoff for the proportion of epithelioid cells has not been defined.[3] eGBs have a wide range of morphological differential diagnosis that include both metastasis and primary astrocytic neoplasms such as anaplastic pleomorphic xanthoastrocytoma, giant cell GB, and rhabdoid GB. In the present case, the cerebellar presentation led to the suspicion of atypical teratoid/rhabdoid teratoid and adult medulloblastoma.

Anaplastic pleomorphic xanthoastrocytoma is a WHO Grade III astrocytic neoplasm that mimics eGB. Although BRAF V600E mutation is also observed in this tumor, however, anaplastic pleomorphic xanthoastrocytoma is excluded from the diagnosis based on the following findings: absence of large pleomorphic and multinucleated cells, xanthomatous change, and no pericellular reticulin deposition.[4] The giant cell Gb is an IDH wild-type GB and is characterized by bizarre multinucleated giant cells and diffuse nuclear reactivity for p53, which was absent in our case.[5]

Rhabdoid GB has not been included in the 2016 WHO classification of CNS tumors as a separate entity. The characteristic rhabdoid cells with epithelioid cells are now placed under the category of eGB.[6] Moreover, the loss of INI 1 protein expression in rhabdoid GBs distinguishes them from similar appearing eGBs. Our case showed complete retention of INI 1 expression in tumor cells.

Large-cell/anaplastic variants of medulloblastoma were excluded from the differential diagnosis because of the absence of sheets of undifferentiated tumor cells and lack of immunoreactivity for neuronal markers.[7] Atypical teratoid/rhabdoid tumor is a malignant CNS embryonal tumor with rhabdoid phenotype and primitive neuroectodermal, mesenchymal, and epithelial features, which were not observed in the present case. Furthermore, typical radiological findings along with the absence of immunoreactivity of tumor cells for epithelial markers ruled out metastasis.

The aggressive behavior and overall poor prognosis of GB, especially for the eGB variant, in young adults have led to the exploration of various treatment strategies such as the targeted inhibitory antibody therapy using BRAF inhibitors.[8] The prognostic and predictive role of tumor-infiltrating lymphocytes is also being examined, and immunotherapy for these tumors is currently under research.[9]


  Conclusion Top


We report a rare case of cerebellar eGB. The case findings highlight the importance of carefully interpreting morphological and immunohistochemical examination findings to diagnose rare variants of GB in an uncommon body part of young adults.

Financial support and sponsorship

Nil.

Institutional review board statement

We have only diagnosed this case. It does not involve any kind of research activity or clinical trial. So ethics approval is not required.

Declaration of patient consent

The authors certify that they have obtained the appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal his identity.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, et al. Diffuse astrocytic and oligodendroglial tumors. WHO Classification of Tumours of the Central Nervous System. Revised 4th ed. Lyon; IARC Press; 2016. p. 16-77.  Back to cited text no. 1
    
2.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 2
    
3.
Chatterjee D, Radotra BD, Aggarwal D, Madan R, Gupta SK. Analysis of 24 cases of epithelioid glioblastoma: Experience from a tertiary centre of North India. Ann Diagn Pathol 2021;50:151679.  Back to cited text no. 3
    
4.
Asano K, Miyamoto S, Kubo O, Kikkukawa T, Yagihashi A, Ohkuma H. A case of anaplastic pleomorphic xanthoastrocytoma presenting with tumor bleeding and cerebrospinal fluid dissemination. Brain Tumor Pathol 2006;23:55-63.  Back to cited text no. 4
    
5.
Shrestha S, Homagain S, Raut A, Sedhain G, Bhatta S, Shrivastav S. Giant cell glioma in 6-year-old kid: Report of an unusual case. Clin Case Rep 2020;8:2936-40.  Back to cited text no. 5
    
6.
Sugimoto K, Ideguchi M, Kimura T, Kajiwara K, Imoto H, Sadahiro H, et al. Epithelioid/rhabdoid glioblastoma: A highly aggressive subtype of glioblastoma. Brain Tumor Pathol 2016;33:137-46.  Back to cited text no. 6
    
7.
Leonard JR, Cai DX, Rivet DJ, Kaufman BA, Park TS, Levy BK, et al. Large cell/anaplastic medulloblastomas and medullomyoblastomas: Clinicopathological and genetic features. J Neurosurg 2001;95:82-8.  Back to cited text no. 7
    
8.
Brown NF, Carter T, Kitchen N, Mulholland P. Dabrafenib and trametinib in BRAFV600E mutated glioma. CNS Oncol 2017;6:291-6.  Back to cited text no. 8
    
9.
Orrego E, Castaneda CA, Castillo M, Bernabe LA, Casavilca S, Chakravarti A, et al. Distribution of tumor-infiltrating immune cells in glioblastoma. CNS Oncol 2018;7:CNS21.  Back to cited text no. 9
    


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