Clinicopathological characteristics and treatment of rhabdoid glioblastoma

Clinical article

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Object

Rhabdoid glioblastoma (GB) is an exceedingly rare tumor in which some of the tumor cells possess rhabdoid features such as eccentric nuclei, abundant eosinophilic cytoplasm, and pseudopapillary formations. These tumors are exceptionally aggressive, and leptomeningeal dissemination is common. In the 9 previously reported cases, the longest survival was only 9 months, with a median survival of 17.8 weeks. The authors report the clinicopathological characteristics of 4 cases of rhabdoid GB and demonstrate the utility of intensive temozolomide and adjuvant therapy in these tumors. The authors also review the literature to provide the most comprehensive understanding of these rare tumors to date.

Methods

A retrospective review was performed of patients treated for GB at the Duke University Medical Center between 2004 and 2012. One of two experienced neuropathologists identified 4 cases as being rhabdoid GBs. Immunohistochemistry and fluorescence in situ hybridization analyses were performed in all cases. Kaplan-Meier analysis was used to assess overall survival, with the log-rank test being used to evaluate differences between survival curves. An extensive review of the literature was also performed.

Results

The median age of patients with rhabdoid GB was 30 years. Clinical presentation varied with location, with headache being a presenting symptom in 90% of patients. All lesions were supratentorial, and 45.5% of the cases involved the temporal lobe. Leptomeningeal dissemination occurred in 63.6% of patients, with 1 patient having extracranial metastasis to the scalp and lungs. Fluorescence in situ hybridization revealed epidermal growth factor receptor gain or amplification in all study cases. The median survival in the authors' cohort was significantly higher than that of all previously reported cases (27.5 vs 4.5 months, p = 0.003). Postoperative treatment in the authors' cohort included radiotherapy with concurrent temozolomide, bevacizumab, interleukin 13, CCNU, and/or etoposide.

Conclusions

Enhanced survival in the authors' 4 patients suggests that the current standard of care for the treatment of GB may be beneficial in rhabdoid GB cases, with postoperative radiotherapy and concomitant temozolomide treatment followed by adjuvant therapy. Due to the rapid tumor dissemination associated with these lesions, aggressive and timely therapy is warranted, with frequent surveillance and/or continued therapy despite stable disease. Additionally, patients should undergo full craniospinal imaging to monitor the development of distant metastatic disease.

Abbreviations used in this paper:EGFR = epidermal growth factor receptor; EMA = epithelial membrane antigen; FISH = fluorescence in situ hybridization; GB = glioblastoma; GFAP = glial fibrillary acidic protein; IL = interleukin; INI-1 = integrase interactor–1; MGMT = O6-methylguanine-DNA methyltransferase; NFP = neurofilament protein; PDGFR = platelet-derived growth factor receptor; PTEN = phosphatase and tensin homolog.

Article Information

Mr. Babu and Mr. Hatef contributed equally to this work.

Address correspondence to: Cory Adamson, M.D., Division of Neurosurgery, DUMC Box 2624, Durham, North Carolina 27710. email: cory.adamson@duke.edu.

Please include this information when citing this paper: published online May 3, 2013; DOI: 10.3171/2013.3.JNS121773.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Case 1. A: T1-weighted MR image demonstrating a heterogeneous hypointense left frontal mass. B: T2-weighted image demonstrating a heterogeneous isointense lesion with perilesional edema. C: T1-weighted Gd-enhanced image demonstrating a ring-enhancing tumor.

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    Case 1. A: Postoperative T1-weighted MR image demonstrating blood products within the posterior aspect of the resection cavity. B: T1-weighted Gd-enhanced image demonstrating residual tumor adjacent to the left lateral ventricle. C: Coronal T1-weighted image showing the residual tumor mass in the medial aspect of the resection cavity. D: T1-weighted image at 6-month follow-up showing the resection cavity. E: Contrast-enhanced T1-weighted image at 6-month follow-up demonstrating marked response to therapy with only 2 nodules of enhancement along the resection cavity suspicious for residual tumor. F: Coronal T1-weighted image at 6-month follow-up showing significant reduction in residual tumor and only a small area of enhancement in the posterolateral aspect of the resection cavity.

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    Case 1. A: The tumor cells, which have large eccentric lobules of deeply eosinophilic cytoplasm, are seen to aggregate around a blood vessel to form a pseudopapillary formation. H & E, original magnification ×40. B–D: FISH revealing a gain in wild-type EGFR copy number, a gain in MET copy number, and a loss of PTEN copy number.

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    Case 4. Tumor cells of rhabdoid GB demonstrating intact INI-1 expression. Anti–INI-1, original magnification ×40.

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    Kaplan-Meir survival curves demonstrating significantly longer survival in the current cohort compared with previously reported cases, reflecting the efficacy of temozolomide and intensive adjuvant therapy for rhabdoid GB.

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