Glioblastoma (GBM) rarely presents as an infratentorial tumor in adults. The authors present a case of concomitant supratentorial and infratentorial GBM in an adult. A 72-year-old man presented with headache, nausea, vomiting, and lightheadedness. Initial MR images revealed enhancing masses in the right cerebellum and right posterior periventricular region. The patient underwent a suboccipital craniotomy and resection of the cerebellar lesion. Final histopathology was consistent with glioblastoma. The patient went on to receive standard radiation treatment for GBM with concurrent and adjuvant temozolomide. However, the patient experienced clinical deterioration within a few days after starting radiotherapy. He and his family decided to forego treatment and pursue palliative care. The patient expired three months after the initial diagnosis. Autopsy findings supported the diagnosis of GBM with leptomeningeal gliomatosis and involvement of the cerebrum, cerebellum, and spinal cord. The authors review the literature and propose that the pathogenesis of multiple and multicentric GBM may involve neural stem cells within the subventricular zone or could result from tumor dissemination along established CNS routes, such as white matter tracts and CSF pathways.
Glioblastoma (GBM) is the most common intraparenchymal primary brain tumor, representing approximately 30% of all brain tumors and 50% of astrocytomas [
Multiple gliomas were first observed by Virchow in 1864 and Bradley in 1880 [
Here, we report a case of a multifocal and multicentric GBM involving the supratentorial and infratentorial regions in an adult and review the literature on all previously documented cases. We also discuss the pathogenesis of this unique presentation of GBM, thereby providing greater insight into the origin and growth of GBM. This insight may lead to changes to the treatment approach of this rare presentation of GBM.
A 72-year-old right-handed male presented to the Emergency Department with headache, nausea, vomiting, and lightheadedness of approximately one week duration. On neurological examination, the patient was intact without any focal deficits. Computed tomography (CT) of the head showed multifocal areas of cerebral edema with areas of abnormal increased attenuation, predominantly involving the right cerebellar hemisphere and adjacent to the right lateral ventricle posteriorly. The cerebellar edema was associated with mass effect on the fourth ventricle and obstructive hydrocephalus. These findings were most suspicious of brain metastases. Subsequent magnetic resonance (MR) imaging of the brain with and without contrast revealed enhancing masses in the right cerebellum measuring
Preoperative MR imaging. (a) Axial T1-weighted image with contrast at the level of the cerebellum showing an enhancing mass in the right cerebellar hemisphere measuring
The patient underwent a suboccipital craniotomy and resection of the cerebellar lesion. Final histopathology was consistent with glioblastoma (Figure
Photomicrographs displaying pathognomonic histopathological features of glioblastoma. (a) Microvascular proliferation with endothelial layer hyperplasia. (b) Areas of geographic necrosis are present. (c) Microscopic examination reveals a hypercellular neoplasm with large, hyperchromatic, pleomorphic cells with cerebellar granular layer cells on the left. (d) Mitotic figures are readily identified in a background of pleomorphic, hyperchromatic neoplastic cells. H&E; original magnification ×10 (a), ×10 (b), ×10 (c), and ×40 (d).
Photomicrograph demonstrating results of GFAP immunohistochemical staining. The neoplastic cells are strongly positive for GFAP immunostain. Original magnification ×40.
Postoperative MR imaging showed leptomeningeal enhancement within the Sylvian fissures and diffuse FLAIR signal abnormality within bilateral cerebral hemispheres (Figure
Postoperative MR imaging. (a) Axial T1-weighted image with contrast at the level of the cerebellum displaying subtotal resection of the tumor within the right cerebellar hemisphere. (b) Axial T1-weighted image with contrast at the level of the Sylvian fissures showing leptomeningeal enhancement. (c) Axial FLAIR image above the tentorium revealing diffuse FLAIR signal abnormality within bilateral cerebral hemispheres.
Autopsy findings supported the diagnosis of GBM with leptomeningeal gliomatosis and involvement of the cerebrum, cerebellum, spinal cord, neurohypophysis, and choroid plexus. In particular, two grossly separate lesions were present within the right hemisphere of the cerebrum, adjacent to the occipital horn of the right lateral ventricle, which were microscopically connected by infiltrating tumor cells and were consistent with GBM (Figure
Gross autopsy image. A coronal section of the brain showing two grossly distinct, hemorrhagic lesions adjacent to the occipital horn of the right lateral ventricle associated with ventricular compression.
In this paper, we report a case of multifocal and multicentric supratentorial and infratentorial GBM in an adult. Our review of the pertinent literature revealed that only 11 other cases of concomitant supratentorial and infratentorial GBM have been documented. The clinical findings in all published adult cases of supratentorial and infratentorial GBM are summarized in Table
Literature review of studies on concomitant supratentorial and infratentorial glioblastomas in adults*.
Authors and year | Case no. | Age (yrs), sex | Location | Histopathology | Treatment | Overall survival (mos) | ||
---|---|---|---|---|---|---|---|---|
Supratentorial | Infratentorial | Supratentorial | Infratentorial | |||||
Present study | 1 | 72, M | Rt posterior periventricular region | Rt cerebellar hemisphere | Glioblastoma | Glioblastoma | STR, TMZ, and WBXRT | 3 |
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Salunke et al. [ |
2 | 50, M | Rt insula | Cerebellar vermis | Grade II astrocytoma | Glioblastoma | STR, WBXRT | 18 |
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Kotwica and Papierz, 1992 [ |
3 | 53, F | Lt temporal lobe | Cerebellar vermis | Glioblastoma | Pilocytic astrocytoma | GTR | 10 |
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Salvati et al. [ |
4 | 47, M | Rt frontal lobe | Lt cerebellar hemisphere | Glioblastoma | Grade III astrocytoma | Biopsy | 2 |
5 | 42, M | Rt temporal lobe | Pons | Glioblastoma | Glioblastoma | GTR | Postoperative mortality | |
6 | 56, F | Lt frontoparietal lobes | Rt cerebellar hemisphere | Glioblastoma | Glioblastoma | Biopsy, Chemotx, and WBXRT | 7 | |
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Kudo et al. [ |
7 | 74, M | Rt occipital lobe | Rt cerebellar hemisphere | Glioblastoma | Glioblastoma | STR | 2 |
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Bussone et al. [ |
8 | 49, M | Rt thalamus | Rt CPA | Glioblastoma | Glioblastoma | None | 4 |
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Takeda et al. [ |
9 | 56, M | Corpus callosum | Cerebellar vermis | Glioblastoma | Glioblastoma | Unknown | 3 |
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Ishida and Nakagawa [ |
10 | 53, M | Rt frontal lobe | Brainstem | Glioblastoma | Glioblastoma | Unknown | 18 |
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Salles et al. [ |
11 | 24, M | Lt temporal lobe | Lt cerebellar hemisphere | Glioblastoma | Glioblastoma | Unknown | 8 |
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Kijima et al. [ |
12 | 31, M | Rt temporal lobe | Brainstem | Glioblastoma | Glioblastoma | Unknown | 3 |
Previously, multifocal and multicentric GBM have been associated with a worse prognosis than solitary GBM, with median patient survival estimates of 6–8 months after different treatment modalities [
The radiographic appearance of multifocal and multicentric GBM is indistinct from that of metastases, with MR imaging displaying multiple contrast-enhancing masses [
The diagnostic workup for multifocal and multicentric GBM is generally the same as that for solitary GBM. Dissemination of GBM, however, can occur intracranially or throughout the spinal axis [
Multifocal and multicentric GBM do not exhibit any histopathologic characteristics that differentiate them from typical, solitary supratentorial GBM [
Although there is still no unified theory regarding the pathogenesis of multifocal and multicentric GBM, several hypotheses have been developed. According to earlier theories, multicentricity arises from two events [
In addition to the molecular pathways involved in multifocality and multicentricity, studies have correlated the tumor pattern at diagnosis and recurrence with the spatial relationship to the subventricular zone (SVZ) and cortex as seen on MR imaging [
Currently, there are no clear guidelines regarding the optimal management of multifocal and multicentric GBM [
In our case, we describe an adult with concomitant supratentorial and infratentorial GBM. The patient expired three months after the initial diagnosis. Autopsy findings supported the diagnosis of GBM with leptomeningeal gliomatosis. Only 11 such cases have been previously published in the literature. Tumor dissemination could have occurred through seeding of the CSF by the periventricular mass. Alternatively, the supratentorial tumor location at the SVZ could have served as a nidus for dissemination along CNS pathways. Molecular characterization of the tumor with immunohistochemical staining for
Currently, there is no specific treatment protocol for multiple or multicentric GBM. Unfortunately, these patients are often excluded from clinical trials. Our patient had a rapid clinical decline despite standard treatment and elected to forego additional treatment. Whether he may have benefitted from an alternative treatment approach with targeted molecular agents is uncertain.
Our compilation and assessment of the case reports on supratentorial and infratentorial GBM in adults documented to date yield several conclusions. This presentation of GBM is rare. MR imaging characteristics are similar to metastatic tumors and therefore histopathological confirmation is necessary. Concomitant supratentorial and infratentorial GBM has the same histological appearance as that of solitary GBM. Finally, molecular and genetic analysis of these unique tumors may provide insight into their pathogenesis as well as the origin and growth of GBM in general.