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Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics

Doyle, Leona A.; Vivero, Marina; Fletcher, Christopher D. M.; Mertens, Fredrik LU and Hornick, Jason L. (2014) In Modern Pathology 27(3). p.390-395
Abstract
Solitary fibrous tumor (SFT) is composed of spindled to ovoid cells in a patternless architecture with prominent stromal collagen and hemangiopericytoma-like vessels. Some tumors show hypercellularity, nuclear atypia, and significant mitotic activity; the latter feature in particular often portends an aggressive clinical course. SFT can sometimes be difficult to distinguish from other benign mesenchymal tumors and sarcomas. The most characteristic (albeit nonspecific) immunohistochemical finding in SFT is CD34 expression. A NAB2-STAT6 gene fusion, resulting in a chimeric protein in which a repressor domain of NGFI-A binding protein 2 (EGR1 binding protein 2) (NAB2) is replaced with a carboxy-terminal transactivation domain from signal... (More)
Solitary fibrous tumor (SFT) is composed of spindled to ovoid cells in a patternless architecture with prominent stromal collagen and hemangiopericytoma-like vessels. Some tumors show hypercellularity, nuclear atypia, and significant mitotic activity; the latter feature in particular often portends an aggressive clinical course. SFT can sometimes be difficult to distinguish from other benign mesenchymal tumors and sarcomas. The most characteristic (albeit nonspecific) immunohistochemical finding in SFT is CD34 expression. A NAB2-STAT6 gene fusion, resulting in a chimeric protein in which a repressor domain of NGFI-A binding protein 2 (EGR1 binding protein 2) (NAB2) is replaced with a carboxy-terminal transactivation domain from signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), was recently identified as a consistent finding in SFT. However, as these genes are located in close proximity on 12q13, this fusion can only rarely be detected by conventional chromosomal banding or fluorescence in situ hybridization analysis. Nuclear expression of the carboxy terminal part of STAT6 is a consistent finding in SFT of the meninges (so-called 'meningeal hemangiopericytoma'). We investigated STAT6 expression by immunohistochemistry in SFTs and other soft tissue tumors arising outside the central nervous system to validate the diagnostic utility of this novel marker. Whole-tissue sections of 231 tumors were evaluated, including 60 cases of SFT as well as other benign and malignant mesenchymal neoplasms and sarcomatoid mesotheliomas. Fifty-nine of 60 SFT cases (98%) showed nuclear expression of STAT6, which was usually diffuse and intense. All other tumor types were negative for STAT6, except for three dedifferentiated liposarcomas and one deep fibrous histiocytoma, which showed weak staining. In conclusion, STAT6 is a highly sensitive and almost perfectly specific immunohistochemical marker for SFT and can be helpful to distinguish this tumor type from histologic mimics. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
gene fusion, immunohistochemistry, sarcoma, soft tissue tumors, whole-exome sequencing
in
Modern Pathology
volume
27
issue
3
pages
390 - 395
publisher
Nature Publishing Group
external identifiers
  • wos:000332426200007
  • scopus:84896711912
ISSN
1530-0285
DOI
10.1038/modpathol.2013.164
language
English
LU publication?
yes
id
faaa5817-8127-427b-8a1a-aaeeb0cf781b (old id 4417714)
date added to LUP
2014-05-05 07:21:16
date last changed
2017-11-19 03:44:07
@article{faaa5817-8127-427b-8a1a-aaeeb0cf781b,
  abstract     = {Solitary fibrous tumor (SFT) is composed of spindled to ovoid cells in a patternless architecture with prominent stromal collagen and hemangiopericytoma-like vessels. Some tumors show hypercellularity, nuclear atypia, and significant mitotic activity; the latter feature in particular often portends an aggressive clinical course. SFT can sometimes be difficult to distinguish from other benign mesenchymal tumors and sarcomas. The most characteristic (albeit nonspecific) immunohistochemical finding in SFT is CD34 expression. A NAB2-STAT6 gene fusion, resulting in a chimeric protein in which a repressor domain of NGFI-A binding protein 2 (EGR1 binding protein 2) (NAB2) is replaced with a carboxy-terminal transactivation domain from signal transducer and activator of transcription 6, interleukin-4 induced (STAT6), was recently identified as a consistent finding in SFT. However, as these genes are located in close proximity on 12q13, this fusion can only rarely be detected by conventional chromosomal banding or fluorescence in situ hybridization analysis. Nuclear expression of the carboxy terminal part of STAT6 is a consistent finding in SFT of the meninges (so-called 'meningeal hemangiopericytoma'). We investigated STAT6 expression by immunohistochemistry in SFTs and other soft tissue tumors arising outside the central nervous system to validate the diagnostic utility of this novel marker. Whole-tissue sections of 231 tumors were evaluated, including 60 cases of SFT as well as other benign and malignant mesenchymal neoplasms and sarcomatoid mesotheliomas. Fifty-nine of 60 SFT cases (98%) showed nuclear expression of STAT6, which was usually diffuse and intense. All other tumor types were negative for STAT6, except for three dedifferentiated liposarcomas and one deep fibrous histiocytoma, which showed weak staining. In conclusion, STAT6 is a highly sensitive and almost perfectly specific immunohistochemical marker for SFT and can be helpful to distinguish this tumor type from histologic mimics.},
  author       = {Doyle, Leona A. and Vivero, Marina and Fletcher, Christopher D. M. and Mertens, Fredrik and Hornick, Jason L.},
  issn         = {1530-0285},
  keyword      = {gene fusion,immunohistochemistry,sarcoma,soft tissue tumors,whole-exome sequencing},
  language     = {eng},
  number       = {3},
  pages        = {390--395},
  publisher    = {Nature Publishing Group},
  series       = {Modern Pathology},
  title        = {Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics},
  url          = {http://dx.doi.org/10.1038/modpathol.2013.164},
  volume       = {27},
  year         = {2014},
}