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| CASE REPORT |
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| Year : 2021 | Volume
: 4
| Issue : 2 | Page : 61-66 |
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Multicentric anaplastic oligodendroglioma involving supra- and infratentorial regions: Glioma aplenty!
Abhinith Shashidhar1, Shilpa Rao2, Jitender Saini3, AS Uday Krishna4, Vani Santosh2, Arimappamagan Arivazhagan1
1 Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, India
2 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, India
3 Department of Neuroradiology, National Institute of Mental Health and Neurosciences, Bengaluru, India
4 Kidwai Memorial Institute of Oncology, Bengaluru, India
| Date of Submission | 28-Sep-2021 |
| Date of Acceptance | 16-Feb-2022 |
| Date of Web Publication | 20-Apr-2022 |
Correspondence Address:
Dr. Arimappamagan Arivazhagan
Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/IJNO.IJNO_21_21
Background: Multicentric gliomas are an uncommon entity and are mostly of astrocytic lineage and rarely oligodendrogliomas (ODGs). Multicentric ODGs are very rare, mostly comprising of two to three lesions. Here, we describe a case of multicentric ODG, with varying histological grades with at least six distinct lesions involving six different regions of the brain.Case Report: A 33-year-old gentleman presented with features of raised intracranial pressure and acute onset altered sensorium. Magnetic resonance imaging (MRI) of the brain revealed multiple lesions involving both cerebral (bilateral frontal and temporal lobes) and cerebellar hemispheres. The patient underwent surgical decompression of two of the lesions which were causing significant mass effect, after which his symptoms improved. Interestingly, both lesions demonstrated ODG histology but with different grades, with one being Grade II and the other being a Grade III lesion. Following surgery, he received adjuvant radiotherapy and chemotherapy with temozolomide. His follow-up MRI brain performed 5 months after surgery showed no recurrence at the operated sites and no increase in size of the remaining lesions.Conclusion: Surgical management of multicentric glioma needs individualized strategy with multidisciplinary care and involves maximal safe resection of large tumors with consideration of biopsy from smaller lesions for histomolecular diagnosis and adjuvant therapy. Keywords: Anaplastic oligodendroglioma, glioma surgery, multicentric glioma, multidisciplinary care, multiple oligodendroglioma
How to cite this article:
Shashidhar A, Rao S, Saini J, Uday Krishna A S, Santosh V, Arivazhagan A. Multicentric anaplastic oligodendroglioma involving supra- and infratentorial regions: Glioma aplenty!. Int J Neurooncol 2021;4:61-6 |
| Introduction | |  |
While multiple meningiomas are very common in neurofibromatosis, there are a few instances of multiple gliomas in some patients, most of them belonging to astrocytic lineage. However, multicentric oligodendroglioma (ODG) is an extremely rare entity, with very few cases reported in literatures.[1],[2] Most multicentric gliomas have presented with two to three lesions synchronously in the imaging in literature. In this report, we present the first case of anaplastic ODG in a young adult, with more than six lesions, involving six regions (bilateral frontal, bilateral temporal, and bilateral cerebellar hemispheres), in the literature, to the best of our knowledge. We discuss the pathogenesis, surgical management dilemmas in decision-making, and factors influencing survival in these rare tumors.
| Case report | | |
A 33-year-old man presented to us with features suggestive of raised intracranial pressure (ICP), namely, diffuse holocranial headache and vomiting for 2 months, with acute exacerbation of symptoms and altered sensorium for 1 week. On initial neurological examination, the patient was drowsy, not obeying to request, localizing to pain, and moving all four limbs against gravity. He was evaluated with an urgent computed tomography (CT) brain with contrast, which revealed multiple intracranial lesions in bilateral (B/L) frontal lobes and right temporal lobe with perilesional edema. Well-demarcated multiple gyriform calcifications were associated with these lesions. There was no significant contrast enhancement [Figure 1]. The patient was treated with anti-edema measures which resulted in the improvement of sensorium. A magnetic resonance imaging (MRI) brain revealed that multiple lesions were present involving nearly all lobes: right and left frontal, right temporal, left temporal, and three to four small lesions in both cerebellar hemispheres [Figure 2]. These lesions were hypointense on T1-weighted images [Figure 2(a)] and (b)] and hyperintense on T2 [[Figure 2(c)]-(e)] with no diffusion restriction. Only the left frontal lesion showed minimal enhancement on post-gadolinium studies [[Figure 2(f)]. The lesions in both frontal and right temporal lobes were large and caused mass effect. The left frontal lesion was the largest with subfalcine herniation. The right temporal lesion was also causing mild uncal prominence on the same side. The left occipital region showed evidence of infarct probably secondary to raised ICP-induced herniation. The imaging features were suggestive of neoplastic etiology, possibly ODG, in view of calcification. | Figure 1: (a-c): CT brain plain and contrast images showed bilateral frontal and right temporal lesions with gyriform pattern of calcifications and perilesional edema
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 | Figure 2: MRI brain showed multiple lesions involving right and left frontal, right temporal, left temporal lobes with three to four small lesions in both cerebellar hemispheres. These lesions were hypo- to heterointense on T1-weighted images (a and e) and hyperintense on T2-weighted images (b-d). Portion of the left frontal lesion showed minimal enhancement on contrast studies (f). Signal changes in the left occipital region were due to infarct secondary to herniation. Follow-up MRI brain axial T2-weighted images performed 5 months after surgery showed post-operative signal changes in the left frontal and right temporal lobes with no recurrence. The remaining lesions in the left temporal and posterior fossa showed no increase in size
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In view of multiple lesions, features of raised ICP, and evidence of herniation, the surgical options were discussed. As there were large lesions, surgical decompression of the tumor was planned to reduce the ICP, although the feasibility of gross total/near total resection of the disease did not exist due to diffuse multilobar involvement of brain. He initially underwent an emergent left frontal craniotomy and near total decompression of the left frontal lesion. He recovered well from the surgery and was conscious, obeying commands post-operatively with no limb deficits. After a period of 2 weeks, he underwent right temporal craniotomy, temporal lobectomy, and gross total decompression of the right temporal lesion.
| Pathology | | |
Histopathological examination of the surgical specimen from the left frontal [Figure 3] and right temporal lesions [Figure 4] revealed features of a diffuse glioma, infiltrating gray and white matter. The tumor cells were arranged in nodules and sheets composed of predominantly oligodendroglial cells with perinuclear halo. The tumor cells were interspersed with thin-walled branching capillaries. Other features seen were subpial carpeting, perineuronal satellitosis, and calcification. In the left frontal tumor, mitosis was sparse, whereas the right temporal tumor revealed increased cellularity and frequent mitoses. | Figure 3: The histopathological sections from left frontal lesion showed oligodendroglial cells arranged in sheets separated by thin-walled blood vessels (×200) (a). These tumor cells were Olig2 (b, ×200) and IDH1R132H (c, ×200)-positive, showed retained nuclear expression of ATRX (d, ×200), and p53-negative (e, ×100). The proliferation was low (f, MIB1, ×200), thereby rendering a diagnosis of Grade II ODG
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 | Figure 4: Histopathological sections from right temporal lesion showed cellular glial tumor (a, H&E ×100), which were IDH1R132H-positive (b, ×100) and showed retained expression of ATRX (c, ×200) and high proliferation (d, MIB-1, ×200), thereby rendering a diagnosis of Grade III anaplastic ODG. Fluorescent in-situ hybridization (FISH) assay for 1p/19q co-deletion showed 1p/19q co-deletion in both tumors (e and f)
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On immunohistochemistry, tumor cells from both the specimens showed cytoplasmic positivity for IDH1R132H, retained ATRX immunoreactivity, and immunonegativity for p53 [Figures 3(c)]-(e) and 4(b) and (c)].
To confirm the diagnoses of ODG, fluorescent in-situ hybridization assay for 1p/19q codeletion was performed in both specimens, which showed 1p/19q co-deletion in both tumors [[Figure 4(e)] and (f)]. Therefore, a final diagnosis of IDH mutant and 1p/19q co-deleted ODG (Grade II and Grade III) was made.
After a multi-disciplinary tumor board discussion, it was decided to treat the remnant lesions with adjuvant radio-chemotherapy as they were small and involved multiple regions of the brain. He received whole brain radiotherapy with a biologically effective dose of 45 Gy followed by a boost of 60 Gy along with concurrent temozolomide therapy and was started on adjuvant temozolomide after a month. He was doing well on follow-up after 2 months of adjuvant therapy with minimal symptoms and a Karnofsky Performance Scale index of 90. A repeat MRI 5 months after surgery showed no recurrence at the previously operated sites with no increase in size of the remaining lesions [[Figure 2(g)] and (h)] and he is planned for regular follow-up.
| Discussion | | |
Multiple gliomas are a well-recognized but uncommon entity with an incidence ranging from 0.5% to 20% across various series.[2 Most of the information on multiple glioma are available as case reports or small series. The multiple gliomas are often named as multifocal or multicentric],[ based on the possibility of synchronous separate origin or a likely continuity and spread.[3] Multifocal gliomas are considered to occur as a result of seeding of the tumor cells by local extension or along commissural pathways, cerebrospinal fluid channels, or blood. On the contrary, multicentric gliomas are considered separate entities which are widely separated from each other, involving different lobes and their occurrence cannot be explained by the aforementioned pathways. The multitude of lesions in our case involving multiple lobes favors a diagnosis of multicentric lesion.
The exact pathogenesis of multicentric glioma is unknown. Hayes et al.[4] analyzed the molecular characteristics of four multicentric low-grade gliomas (LGGs). They noted that each tumor in multicentric glioma can arise independently or may diverge very early in development, resulting in histologically and genetically distinct tumors. Some of them can carry a germline mutation too, necessitating a comprehensive biopsy and molecular analysis in these tumors.
Even though multicentric gliomas have been reported in literature, they are commonly astrocytomas or glioblastomas.[5],[6],[7],[8] Wang et al.[9],[10] published two series on multicentric gliomas: one analyzing the low grade tumors and the other addressing the factors influencing survival in high-grade glioma (HGG). Among 36 cases of multicentric LGGs, there were seven patients with oligodendroglial tumor and the number of tumors in each patient ranged from 2 to 4.[10] Multicentric anaplastic ODGs are a rare entity with only few case reports available in the literatures.[1],[2] In a series of 73 cases of multicentric HGGs collated from published literature by Wang et al.,[9] they noted that none of them was anaplastic ODG. In addition, there was only one patient who harbored six lesions, with most patients having two to four tumors.
Interestingly, we noted that our patient had at least seven distinct lesions, involving six regions (bilateral frontal, bilateral temporal, and bilateral cerebellar hemispheres). Two of the lesions, distinct from each other, one involving left frontal and other involving right temporal, have demonstrated ODG histology, with one being Grade II and the other being Grade III lesion, respectively. This is the first case of anaplastic ODG in a young adult, with more than six lesions, involving more than two hemispheres, in the literature, to the best of our knowledge.
Among the multicentric LGGs, younger age, oligodendroglial histology, and pure low-grade histology were associated with higher progression free survival on univariate analysis. None of the factors influenced overall survival in the multivariate analysis. IDH1 mutations are usually seen in LGGs and are retained during tumor progression. The presence of an IDH1 mutation suggests a better prognosis than tumors with IDH wild-type.[10] Among the multicentric HGGs, younger age, surgical resection, and radiotherapy were associated with better overall survival.[9]
There are no clear guidelines for the management of multicentric gliomas. The following features need to be considered while deciding on the management plan. The multiple lesions can be different in histology and grade of the tumor, as seen in our case as well as in the published literature.[9],[10] Even with the same histology and grade, tumors can show different biological behaviors and tendency to recur.[11] The molecular pathogenesis of multicentric glioma can involve diverse genetic and genetic alterations and cannot be generalized.[4]
Many authors have considered only stereotactic biopsy of one or more lesions to confirm diagnosis in view of diffuse disease and further treated with radiotherapy and chemotherapy. This approach may be relevant when the lesions are small without mass effect. However, as shown by Wang et al., surgical resection of large lesions can influence survival and therefore should be considered for large lesions. As in our patient, it is advisable to resect all the lesions causing mass effect and perform micromolecular analysis. If the lesions are small, multiple biopsies from lesions with radiological diversity are to be considered. In large lesions, the aim of surgery should be to perform a maximal safe resection of most of the accessible lesions without causing any additional neurological deficit. In our patient, we resected two of the largest lesions which were causing significant mass effect causing herniation and considered adjuvant therapy for the remaining small and deep-seated lesions. Prognosis generally depends on the grade and molecular profile of the lesions and response to adjuvant therapy.
| Conclusion | | |
Multicentric gliomas are a rare entity, which can demonstrate different histologies and grades of tumor. Multicentric anaplastic ODG involving six regions of brain is extremely rare. Surgical management of these tumors should involve maximal safe resection of large tumors and consideration of biopsy from multiple lesions for histomolecular diagnosis and adjuvant therapy. Further molecular profiling and pathway analysis of these rare tumors can provide insight into origin of multicentric glioma.
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| 10. | Wang T, Yang Y, Xu X, Niu X, Yang R, Gao T, et al. An integrative survival analysis for multicentric low-grade glioma. World Neurosurg 2020;134:e189-95. |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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