Epithelial and pseudoepithelial differentiation in glioblastoma and gliosarcoma

A comparative morphologic and molecular genetic study

Fausto J. Rodriguez, Bernd W. Scheithauer, Caterina Giannini, Sandra C. Bryant, Robert Brian Jenkins

Research output: Contribution to journalArticle

55 Citations (Scopus)

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/213q (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.

Original languageEnglish (US)
Pages (from-to)2779-2789
Number of pages11
JournalCancer
Volume113
Issue number10
DOIs
StatePublished - Nov 15 2008

Fingerprint

Gliosarcoma
Glioblastoma
Molecular Biology
Adenoids
Epidermal Growth Factor Receptor
Immunohistochemistry
Fluorescence In Situ Hybridization
Staining and Labeling
Neoplasms
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 7
Hematoxylin
Eosine Yellowish-(YS)
Chromosome Aberrations
Sarcoma

Keywords

  • Adenoid
  • Brain
  • Epithelial
  • Epithelioid
  • Fluorescent in situ hybridization
  • Glioblastoma
  • Glioma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Epithelial and pseudoepithelial differentiation in glioblastoma and gliosarcoma : A comparative morphologic and molecular genetic study. / Rodriguez, Fausto J.; Scheithauer, Bernd W.; Giannini, Caterina; Bryant, Sandra C.; Jenkins, Robert Brian.

In: Cancer, Vol. 113, No. 10, 15.11.2008, p. 2779-2789.

Research output: Contribution to journalArticle

@article{9df87227ac6e4af385541b0725b84d9e,
title = "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/213q (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.",
keywords = "Adenoid, Brain, Epithelial, Epithelioid, Fluorescent in situ hybridization, Glioblastoma, Glioma",
author = "Rodriguez, {Fausto J.} and Scheithauer, {Bernd W.} and Caterina Giannini and Bryant, {Sandra C.} and Jenkins, {Robert Brian}",
year = "2008",
month = "11",
day = "15",
doi = "10.1002/cncr.23899",
language = "English (US)",
volume = "113",
pages = "2779--2789",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "10",

}

TY - JOUR

T1 - Epithelial and pseudoepithelial differentiation in glioblastoma and gliosarcoma

T2 - A comparative morphologic and molecular genetic study

AU - Rodriguez, Fausto J.

AU - Scheithauer, Bernd W.

AU - Giannini, Caterina

AU - Bryant, Sandra C.

AU - Jenkins, Robert Brian

PY - 2008/11/15

Y1 - 2008/11/15

N2 - 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/213q (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.

AB - 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/213q (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.

KW - Adenoid

KW - Brain

KW - Epithelial

KW - Epithelioid

KW - Fluorescent in situ hybridization

KW - Glioblastoma

KW - Glioma

UR - http://www.scopus.com/inward/record.url?scp=55849116363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55849116363&partnerID=8YFLogxK

U2 - 10.1002/cncr.23899

DO - 10.1002/cncr.23899

M3 - Article

VL - 113

SP - 2779

EP - 2789

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 10

ER -