Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics

Our plain-English summary of Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics, by L.A. Doyle, M. Vivero, C.D. Fletcher, et al (Modern Pathology, 2014).

The study

• Authors: L.A. Doyle, M. Vivero, C.D. Fletcher, F. Mertens, J.L. Hornick
• Journal: Modern Pathology
• Published: 2014;27(3):390-5
• Cited by: 592 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This laboratory pathology study, from Brigham and Women's Hospital in Boston and Skåne University Hospital in Lund, Sweden, tested whether a staining test for the protein STAT6 could tell solitary fibrous tumor (SFT), a soft tissue tumor, apart from other tumors that look similar under the microscope. The authors stained tissue from 231 tumors, including 60 SFTs and 10 sarcomatoid mesotheliomas. The study did not look at asbestos or any other exposure. Fifty-nine of the 60 SFTs (98%) showed STAT6 in the cell nucleus, most often strongly. The one SFT that stained negative was malignant and had earlier been shown to carry the NAB2-STAT6 gene fusion. None of the 10 sarcomatoid mesotheliomas stained positive. Among the other comparison tumors, only 3 of 21 dedifferentiated liposarcomas and 1 of 10 deep fibrous histiocytomas showed weak staining. The authors suggested that uneven staining in some tumors may have come from uneven tissue fixation. The authors concluded that STAT6 is a highly sensitive and almost perfectly specific marker for SFT that can help distinguish it from look-alike tumors.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory pathology study testing an immunohistochemical (tissue staining) marker on archived tumor samples
• Who was studied: Whole-tissue sections of 231 tumors from the files of Brigham and Women's Hospital (Boston), Skåne University Hospital (Lund, Sweden) and one author's consult files. These were 60 solitary fibrous tumors and 171 comparison tumors, including 10 sarcomatoid mesotheliomas. Dates of the cases are not given.
• Exposure: Not applicable. No asbestos or other environmental or occupational exposure was studied. The study tested STAT6 immunostaining as a diagnostic marker.
• Main results:
  • Solitary fibrous tumors: 59 of 60 (98%) showed nuclear STAT6 staining.
  • Among the 59 STAT6-positive solitary fibrous tumors, staining intensity was strong in 40, moderate in 15 and weak in 4.
  • The single STAT6-negative solitary fibrous tumor was malignant, was CD34-positive, and had previously been shown to carry the NAB2-STAT6 fusion gene.
  • Of the 59 STAT6-positive solitary fibrous tumors, 4 were negative for CD34 (the older marker), 54 were positive, and 1 had unknown CD34 status.
  • Sarcomatoid mesotheliomas: 0 of 10 were STAT6-positive.
  • Dedifferentiated liposarcomas: 3 of 21 (14%) showed mostly weak STAT6 staining.
  • Deep fibrous histiocytomas: 1 of 10 showed weak STAT6 staining. All other comparison tumor types were negative.
  • Eight non-SFT tumors showed a faint 'blush' of staining without a distinct nuclear pattern and were counted as negative.
• The authors' conclusion: The authors concluded that STAT6 is a highly sensitive and almost perfectly specific immunohistochemical marker for solitary fibrous tumor and can help distinguish it from histologic mimics.
• Limitations the authors state:
  • Some tumors stained unevenly in extent and intensity, which the authors suggested may be due to uneven tissue fixation.

Topics

Medical terms in this study, explained in our Lexicon: Solitary Fibrous Tumor, Collagen, Nuclear Atypia, Mesenchymal Tumor, Sarcoma, CD34, Fluorescence In Situ Hybridization (FISH), Immunohistochemistry.

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• Somatic and visceral solitary fibrous tumors in the abdomen and pelvis: cross-sectional imaging spectrum — A.K. Shanbhogue, S.R. Prasad, et al. (2011)
• Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases — M. Miettinen, Z. Wang, et al. (2015)
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