Abstract

Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs.

Highlights

  • Solitary fibrous tumors (SFT) are mesenchymal neoplasms usually originating from the visceral pleura but can occur at various extrapleural sites [1]

  • The Ki67-positive rate was low, around 1% (Figure 3B), but cells were diffusely stained with CD34 (Figure 3C) and tumor cell nuclei were positively stained with signal transducer and activator of transcription 6 (STAT6) (Figure 3D)

  • We conducted a complete histological examination of the multiple metastatic sites revealed at autopsy, including more than 30 lung metastases, 2 liver metastases, 3 bone metastases and 1 adrenal metastasis, and pathological findings for all sites were similar to the right-side dedifferentiated tumor

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Summary

Introduction

Solitary fibrous tumors (SFT) are mesenchymal neoplasms usually originating from the visceral pleura but can occur at various extrapleural sites [1]. They are usually slow-growing with favorable prognoses but approximately 10-20% develop malignancy [2, 3]. SFTs are diagnosed by histologic features and CD34 immunostaining while positive findings for Bcl-2 and CD99 are supportive for diagnosis [1]. We present a rare case of retroperitoneal SFT where the primary tumor contained a clear delineation between benign (CD34- and STAT6-positive) and malignant (CD34- and STAT6-negative) histologies. We analyze the molecular characteristics of this unique case and discuss mechanisms for the observed malignant phenotype

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