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Solitary fibrous tumor - clinicopathologic, immunohistochemical and molecular analysis of 28 cases.

Vogels RJ, Vlenterie M, Versleijen-Jonkers YM, Ruijter E, Bekers EM, Verdijk MA, Link MM, Bonenkamp JJ, van der Graaf WT, Slootweg PJ, Suurmeijer AJ, Groenen PJ, Flucke U - Diagn Pathol (2014)

Bottom Line: All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.STAT6 immunohistochemistry is another useful tool in diagnosing SFT.EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. rob.vogels@radboudumc.nl.

ABSTRACT

Background: Solitary fibrous tumor is a mesenchymal tumor of fibroblastic type, which can affect any region of the body. Recently, a recurrent gene fusion NAB2-STAT6 has been identified as molecular hallmark. The NAB2-STAT6 fusion leads to EGR1 activation and transcriptional deregulation of EGR1-dependent target genes and is a driving event in initiation of SFT. In this study, we report the clinicopathologic and RT-PCR findings and evaluated expression of STAT6 and EGR1 protein in a cohort of 28 SFTs.

Methods: 28 patients with a median age of 54 years were included with SFTs originating at different sites, most occurring in the lung and pleura (9, 32%), 5 in soft tissues of the lower extremities (18%) and 5 in the head and neck (18%). For detection of the NAB2-STAT6 fusion gene, RT-PCR was performed using RNA extracted from formalin-fixed and paraffin-embedded tissues. Immunohistochemistry was performed on all cases with antibodies against STAT6 and EGR1.

Results: All patients were treated by surgery, 3 with adjuvant chemo- or radiotherapy. Follow-up data of 18 patients could be obtained of which 2 patients died of metastatic disease 13 months and 52 years after first diagnosis. Sixteen patients have no evidence of disease with a median follow up of 29.5 months (range 7 - 120 months). NAB2-STAT6 fusion transcripts were found in 19/28 cases (68%). The most common fusion was between NAB2 exon 4 and STAT6 exon 3 (11/19, 58%), mainly occurring in pleuropulmonary lesions. All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.

Conclusions: The identification of the NAB2-STAT6 fusion in SFTs can provide important diagnostic information, especially in cases with aberrant morphology or when biopsy material is limited. STAT6 immunohistochemistry is another useful tool in diagnosing SFT. EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_224.

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Typical features of SFT visible in all cases (A, HE 10x) and immunohistochemical positive staining of CD34 (B, 10x).
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Fig1: Typical features of SFT visible in all cases (A, HE 10x) and immunohistochemical positive staining of CD34 (B, 10x).

Mentions: Histologically, most of the tumors were circumscribed and a (incomplete) pseudo capsule was sometimes detected. In few cases, focal infiltration of adjacent structures was seen. All cases showed typical features of SFT with a patternless architecture of alternating hypo- and hyper cellular areas of spindle-shaped cells (Figure 1A). A round cell component was found in 2 cases (case 17 and recurrences of case 1). The latter case showed additionally a fascicular growth pattern in the recurrences. The nuclei were relatively uniform, spindled or oval-shaped. Nuclear atypia was focally obvious in case 12 and giant cells were detected in case 8. The mitotic rate ranged from 0/10 HPF to 30/10 HPF (with no differences between patients with or without metastatic disease, Table 3). Hemangiopericytoma-like vessels were visible in all cases, partly with hyalinization of the vessel walls. A variable collagenous background was existent and case 5 possessed amianthoid fibers. Pseudocystic changes were seen in myxoid areas of 5 cases and small areas of necrosis were present in 3 cases. Mature adipocytes were a component in 1 case being an example of a morphologically malignant fat-forming SFT which was published previously [15].Figure 1


Solitary fibrous tumor - clinicopathologic, immunohistochemical and molecular analysis of 28 cases.

Vogels RJ, Vlenterie M, Versleijen-Jonkers YM, Ruijter E, Bekers EM, Verdijk MA, Link MM, Bonenkamp JJ, van der Graaf WT, Slootweg PJ, Suurmeijer AJ, Groenen PJ, Flucke U - Diagn Pathol (2014)

Typical features of SFT visible in all cases (A, HE 10x) and immunohistochemical positive staining of CD34 (B, 10x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4264260&req=5

Fig1: Typical features of SFT visible in all cases (A, HE 10x) and immunohistochemical positive staining of CD34 (B, 10x).
Mentions: Histologically, most of the tumors were circumscribed and a (incomplete) pseudo capsule was sometimes detected. In few cases, focal infiltration of adjacent structures was seen. All cases showed typical features of SFT with a patternless architecture of alternating hypo- and hyper cellular areas of spindle-shaped cells (Figure 1A). A round cell component was found in 2 cases (case 17 and recurrences of case 1). The latter case showed additionally a fascicular growth pattern in the recurrences. The nuclei were relatively uniform, spindled or oval-shaped. Nuclear atypia was focally obvious in case 12 and giant cells were detected in case 8. The mitotic rate ranged from 0/10 HPF to 30/10 HPF (with no differences between patients with or without metastatic disease, Table 3). Hemangiopericytoma-like vessels were visible in all cases, partly with hyalinization of the vessel walls. A variable collagenous background was existent and case 5 possessed amianthoid fibers. Pseudocystic changes were seen in myxoid areas of 5 cases and small areas of necrosis were present in 3 cases. Mature adipocytes were a component in 1 case being an example of a morphologically malignant fat-forming SFT which was published previously [15].Figure 1

Bottom Line: All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.STAT6 immunohistochemistry is another useful tool in diagnosing SFT.EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. rob.vogels@radboudumc.nl.

ABSTRACT

Background: Solitary fibrous tumor is a mesenchymal tumor of fibroblastic type, which can affect any region of the body. Recently, a recurrent gene fusion NAB2-STAT6 has been identified as molecular hallmark. The NAB2-STAT6 fusion leads to EGR1 activation and transcriptional deregulation of EGR1-dependent target genes and is a driving event in initiation of SFT. In this study, we report the clinicopathologic and RT-PCR findings and evaluated expression of STAT6 and EGR1 protein in a cohort of 28 SFTs.

Methods: 28 patients with a median age of 54 years were included with SFTs originating at different sites, most occurring in the lung and pleura (9, 32%), 5 in soft tissues of the lower extremities (18%) and 5 in the head and neck (18%). For detection of the NAB2-STAT6 fusion gene, RT-PCR was performed using RNA extracted from formalin-fixed and paraffin-embedded tissues. Immunohistochemistry was performed on all cases with antibodies against STAT6 and EGR1.

Results: All patients were treated by surgery, 3 with adjuvant chemo- or radiotherapy. Follow-up data of 18 patients could be obtained of which 2 patients died of metastatic disease 13 months and 52 years after first diagnosis. Sixteen patients have no evidence of disease with a median follow up of 29.5 months (range 7 - 120 months). NAB2-STAT6 fusion transcripts were found in 19/28 cases (68%). The most common fusion was between NAB2 exon 4 and STAT6 exon 3 (11/19, 58%), mainly occurring in pleuropulmonary lesions. All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.

Conclusions: The identification of the NAB2-STAT6 fusion in SFTs can provide important diagnostic information, especially in cases with aberrant morphology or when biopsy material is limited. STAT6 immunohistochemistry is another useful tool in diagnosing SFT. EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_224.

Show MeSH
Related in: MedlinePlus