Epithelial and pseudoepithelial differentiation in glioblastoma and gliosarcoma: a comparative morphologic and molecular genetic study.

Abstract

BACKGROUND:

Glioblastomas exhibit a remarkable tendency toward morphologic diversity. Although rare, pseudoepithelial components (adenoid or epithelioid) or true epithelial differentiation may occur, posing a significant diagnostic challenge.

METHODS:

Hematoxylin and eosin-stained slides were reviewed, and immunohistochemistry and fluorescence in situ hybridization were performed.

RESULTS:

The patients included 38 men and 20 women. The median age at diagnosis was 57 years (interquartile range [IQR], 50 years-67 years), and the median overall survival was 7 months (IQR, 4 months-11 months). "Adenoid" glioblastomas (A-GBM) predominated (48%). True epithelial glioblastomas (TE-GBM) were next most frequent based on morphology and immunohistochemistry (35%), followed by epithelioid glioblastomas (E-GBM) (17%). Overall, 25 (43%) tumors featured a sarcomatous component. Molecular cytogenetic abnormalities identified by fluorescent in situ hybridization in A-GBM, E-GBM, and TE-GBM, respectively, included p16 deletion/-9 (60%, 71%, 64%); chromosome 10 loss (40%, 63%, 57%), chromosome 7 gain without EGFR amplification (70%, 38%, 40%), EGFR amplification (10%, 50%, 27%), PTEN deletion (10%, 25%, 29%), PDGFRA amplification (10%, 25%, 0%), and RB1 deletion/-13q (50%, 0%, 14%). Abnormalities identified by immunohistochemistry included p21 immunonegativity (60%, 25%, 93%), which was most frequent in TE-GBM (P = .008), strong nuclear p53 staining (29%, 29%, 41%), strong membranous staining for epidermal growth factor receptor (EGFR) (21%, 63%, 19%), which was most frequent in E-GBM (P = .03), and an increased frequency of p27 immunonegativity in gliosarcomas (15% negative, 85% focal) compared with tumors without sarcoma (38% strongly positive) (P = .009).

CONCLUSIONS:

Pseudoepithelial and true epithelial morphology are rare phenomena in GBM and may be associated with a similar poor prognosis. These tumors demonstrate proportions of molecular genetic abnormalities varying somewhat from conventional GBM.

• Authors: Fausto J Rodriguez, Bernd W Scheithauer, Caterina Giannini, Sandra C Bryant, Robert B Jenkins
• Journal: Cancer (Cancer) Vol. 113 Issue 10 Pg. 2779-89 (Nov 15 2008) ISSN: 0008-543X [Print] United States
• PMID: 18816605 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Topics

• Aged
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Differentiation
• Disease-Free Survival
• Female
• Fluorescent Antibody Technique
• Glioblastoma (genetics, metabolism, pathology)
• Gliosarcoma (genetics, metabolism, pathology)
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Tissue Array Analysis