Glioblastoma with Rhabdoid Features: Report of Two Young Adult Cases and Review of the Literature.

BACKGROUND: There are few previous reports of glioblastoma in young adults, in particular, of the very rare recently proposed rhabdoid or epithelioid types. CASE DESCRIPTION: We report 2 cases of glioblastoma with rhabdoid features involving a 27-year-old woman and a 41-year-old man. In case 1, the patient presented with generalized seizures, and the initial magnetic resonance imaging showed a very small region of contrast in the left parahippocampal area. After 1 year, the mass suddenly increased in size. Treatment with multiple therapies was administered, but 5 months later, the patient died from multiple systemic metastases. In case 2, the patient presented with a chief complaint of headache for a few weeks. Computed tomography and magnetic resonance imaging showed a left parietal mass with calcification and meningeal dissemination. After undergoing surgical removal, his condition rapidly deteriorated until brain death occurred. CONCLUSIONS: Glioblastoma with rhabdoid features may represent a specific pattern of clinical progression that emerges from histologic glioblastoma types.

Epithelioid/rhabdoid glioblastoma: a highly aggressive subtype of glioblastoma.

Epithelioid glioblastoma (GBM) and rhabdoid GBM are rare variants that are morphologically similar, but there is no consensus on the characteristics of each disease. These tumors have aggressive features of early recurrence and leptomeningeal dissemination and tend to develop in younger patients compared to typical GBM. The prognosis is normally worse than typical GBM, even with intensive chemoradiotherapy after surgical resection. Thus, accurate diagnosis and effective therapy for epithelioid/rhabdoid GBM are required. Four consecutive patients aged 16-48 years were diagnosed with epithelioid/rhabdoid GBM by pathological and immunohistochemical analysis at Yamaguchi University Hospital from 2006 to 2012. Two of these patients had relatively long-term survival (19 and 23 months after diagnosis). Two cases had a BRAF V600E mutation, whereas no ATRX mutation was present in any cases. All patients suffered leptomeningeal and/or spinal dissemination that worsened their prognosis. These results illustrate the need for a new therapeutic approach, such as molecular targeted drug therapy like BRAF inhibition, in addition to standard chemoradiotherapy for typical GBM.

Rhabdoid glioblastoma: an aggressive variaty of astrocytic tumor.

Rhabdoid glioblastoma (RGBM) is rare, but the most malignant among astrocytic tumors. Accumulating evidence indicates its highly aggressive nature and distinct histopathological features. Here, we report a new case of RGBM and review previously reported cases of astrocytic tumors with rhabdoid components. We describe a 58-year-old man who presented with aphasia and right-sided weakness. Magnetic resonance imaging revealed a well-delineated intramedullary tumor in the left cerebral hemisphere. Partial resection of the tumor was performed. The tumor was histologically found to contain two distinct areas: a typical glioblastoma, and a rhabdoid component. Immunohistochemical analyses revealed expression of glial fibrillary acidic protein (GFAP) and focal loss of the INI1 protein in rhabdoid cells, although fluorescence in situ hybridization analysis showed no loss of the INI1 gene. Despite subsequent radiochemotherapy for the glioblastoma, the patient died 4.3 months after surgery. Our literature review illustrates the aggressive clinical course and histopathological features of these tumors with GFAP and INI1 expression. INI1 protein dysfunction may be a possible cause of the rhabdoid phenotype. Gross total resection of the tumor and intensive radiochemotherapy may lead to better survival outcomes.

Rhabdoid glioblastoma is distinguishable from classical glioblastoma by cytogenetics and molecular genetics.

The clinicopathologic and molecular genetic features of 5 cases of rhabdoid glioblastoma, an extremely rare variant of glioblastoma that tends to affect patients at a young age, were investigated by immunohistochemical analysis and focused molecular genetic studies including array-based comparative genomic hybridization. All 5 cases had supratentorial tumors that immunohistochemical analysis revealed to be robustly positive for epithelial membrane antigen, vimentin, p53, and PDGFRα (platelet-derived growth factor receptor, alpha polypeptide) but only focally positive for glial fibrillary acidic protein. Although complete retention of SMARCB1 (INI1) was observed in all 5 cases, epidermal growth factor receptor (EGFR) amplification, PTEN (phosphatase and tensin homolog) loss, homozygous deletion of cyclin-dependent kinase inhibitor 2A, 1p/19q codeletion, and isocitrate dehydrogenase 1 R132/IDH2 R172 mutation were not observed in any case, although a high level of EGFR polysomy was detected in 1 recurrent tumor. Although c-MET (MET protein) expression was focal but robustly positive in 3 cases, met proto-oncogene (MET) fluorescence in situ hybridization revealed low polysomy but not MET amplification. MGMT (O-6-methylguanine-DNA methyl-40 transferase) methylation-specific polymerase chain reaction revealed MGMT methylation in only 1 case. Furthermore, array-based comparative genomic hybridization revealed gain of chromosome 7 and loss of 1p, 6, 8p, 11, 13q, and 18q but no deletion of chromosome 22. In contrast to the classical subtype of primary glioblastoma, the cases studied here were characterized by the absence of EGFR amplification, PTEN loss, and 9p homozygous deletion and overexpression of p53, PDGFRα, and c-MET, suggesting that they can be classified as the proneural or mesenchymal subtype of glioblastoma and benefit from intensive therapy that includes temozolomide.